If I Have Had Alcohol Seizures Can I Drink Again
| Download this PDF (631 KB) What Happened? Alcohol, Memory Blackouts, and the EncephalonBooze Research & Health. 2003;27(2): 186-96. Aaron M. White, Ph.D.Aaron Grand. White, Ph.D., is an assistant research professor in the Department of Psychiatry, Knuckles University Medical Eye, Durham, North Carolina. This work was supported by the National Found on Alcohol Corruption and Alcoholism grant AA–12478 and the Institute for Medical Research at the VA Medical Center in Durham, North Carolina. |
Alcohol primarily interferes with the ability to form new long–term memories, leaving intact previously established long–term memories and the ability to keep new data active in memory for brief periods. As the amount of booze consumed increases, and so does the magnitude of the retentivity impairments. Big amounts of alcohol, particularly if consumed rapidly, tin can produce partial (i.e., fragmentary) or complete (i.e., en bloc) blackouts, which are periods of retentiveness loss for events that transpired while a person was drinking. Blackouts are much more common among social drinkers—including college drinkers—than was previously assumed, and take been found to encompass events ranging from conversations to intercourse. Mechanisms underlying alcohol–induced memory impairments include disruption of activeness in the hippocampus, a brain region that plays a central function in the formation of new auotbiographical memories. Key words: alcoholic blackout; memory interference; AOD (booze and other drug) intoxication; AODE (alcohol and other drug effects); AODR (alcohol and other drug related) mental disorder; long–term memory; brusque–term memory; state–dependent memory; BAC level; social AOD apply; drug interaction; illness susceptibility; hippocampus; frontal cortex; neuroimaging; long–term potentiation
If recreational drugs were tools, alcohol would be a sledgehammer. Few cerebral functions or behaviors escape the touch on of alcohol, a fact that has long been recognized in the literature. As Fleming stated almost 70 years agone, "the striking and inescapable impression 1 gets from a review of astute alcoholic intoxication is of the almost infinite diversity of symptoms that may ensue from the activity of this unmarried toxic amanuensis" (1935) (pp. 94–95). In addition to impairing balance, motor coordination, decisionmaking, and a litany of other functions, booze produces detectable retentiveness impairments beginning after just one or ii drinks. As the dose increases, and so does the magnitude of the memory impairments. Under certain circumstances, alcohol can disrupt or completely block the power to form memories for events that transpire while a person is intoxicated, a type of impairment known equally a blackout. This commodity reviews what is currently known regarding the specific features of astute alcohol–induced retentiveness dysfunction, particularly alcohol–induced blackouts, and the pharmacological mechanisms underlying them.
EFFECTS OF ALCOHOL ON MEMORY
To evaluate the furnishings of alcohol, or whatsoever other drug, on memory, i must outset identify a model of retentiveness formation and storage to use every bit a reference. One classic, often–cited model, initially proposed by Atkinson and Shiffrin (1968), posits that memory formation and storage have place in several stages, proceeding from sensory retentivity (which lasts upwardly to a few seconds) to short–term retentivity (which lasts from seconds to minutes depending upon whether the data is rehearsed) to long–term storage. This model oft is referred to as the modal model of memory, as it captures central elements of several other major models. Indeed, elements of this model still can be seen in virtually all models of retentiveness germination.
In the modal model of retentivity, when ane attends to sensory data, it is transferred from a sensory retentivity store to short–term memory. The likelihood that data will be transferred from brusque–term to long–term storage, or exist encoded into long–term memory, was once thought to depend primarily on how long the person keeps the information agile in curt–term memory via rehearsal. Although rehearsal clearly influences the transfer of data into long–term storage, information technology is of import to note that other factors, such as the depth of processing (i.e., the level of truthful understanding and manipulation of the data), attention, motivation, and arousal also play important roles (Craik and Lockhart 1972; Otten et al. 2001; Eichenbaum 2002).1 (1 It is well across the scope of this review to assess the impact of alcohol on memory utilizing multiple perspectives on information processing and storage. For simplicity, this review will narrate the furnishings of booze on memory using a three–stage process of memory germination akin to the modal model. The interpretation of the furnishings of alcohol on memory likely would vary somewhat depending on the retentiveness model one uses.)
Variability in the apply of terms, particularly in operational definitions of short–term retentivity, makes it difficult to formulate a unproblematic synopsis of the literature on alcohol–induced memory impairments. Every bit Mello (1973) stated three decades ago with regard to the memory literature in general, "The inconsistent use of descriptive terms has been a recurrent source of confusion in the 'short–term' retentiveness literature and 'brusque–term' memory has been variously defined as 5 seconds, 5 minutes, and 30 minutes" (p. 333). In spite of this inconsistency, several conclusions can be drawn from inquiry on booze–induced memory impairments. One conclusion is that the affect of booze on the formation of new long–term "explicit" memories—that is, memories of facts (e.grand., names and phone numbers) and events—is far greater than the drug's impact on the ability to call back previously established memories or to concord new information in short–term retention (Lister et al. 1991). (Run across figure 1 for a diagram depicting the stages of memory and where alcohol interferes with retentivity.) Intoxicated subjects are typically able to repeat new information immediately after its presentation and often can proceed it agile in brusque–term storage for upward to a few minutes if they are not distracted (for an early review, run across Ryback 1971), though this is non always the case (Nordby et al. 1999). Similarly, subjects normally are capable of retrieving data placed in long–term storage prior to acute intoxication. In dissimilarity, booze impairs the power to store information beyond delays longer than a few seconds if subjects are distracted between the time they are given the new information and the time they are tested. In a classic study, Parker and colleagues (1976) reported that when intoxicated subjects were presented with "paired assembly"—for example, the letter of the alphabet "B" paired with the calendar month "January"—they were impaired when asked to recall the items subsequently delays of a infinitesimal or more. However, subjects could call up paired associates that they had learned before condign intoxicated. More recently, Acheson and colleagues (1998) observed that intoxicated subjects could recall items on word lists immediately subsequently the lists were presented just were impaired when asked to recall the items 20 minutes later.
Figure ane A general model of memory formation, storage, and retrieval based on the modal model of retention originally proposed by Atkinson and Shiffrin (1968). Alcohol seems to influence almost stages of the process to some degree, just its primary effect appears to exist on the transfer of information from short–term to long–term storage. Intoxicated subjects are typically able to recall information immediately subsequently it is presented and even keep it active in brusk–term memory for i minute or more than if they are not distracted. Subjects besides are usually able to recall long–term memories formed before they became intoxicated; nonetheless, beginning with just one or two drinks, subjects begin to evidence impairments in the ability to transfer information into long–term storage. Under some circumstances, alcohol tin impact this process so severely that, once sober once more, subjects are unable to retrieve critical elements of events, or fifty-fifty unabridged events, that occurred while they were intoxicated. These impairments are known every bit blackouts.
Ryback (1971) characterized the impact of alcohol on memory formation as a dose–related continuum, with pocket-sized impairments at one stop and big impairments at the other, all impairments representing the same key deficit in the power to transfer new data from short–term to long–term storage. When doses of alcohol are pocket-sized to moderate (producing blood booze concentrations [BACs] beneath 0.15 percent), memory impairments tend to exist small to moderate as well. At these levels, booze produces what Ryback (1971) referred to as cocktail party memory deficits, lapses in memory that people might experience after having a few drinks at a cocktail party, often manifested as problems remembering what another person said or where they were in conversation. Several studies take revealed that alcohol at such levels causes difficulty forming memories for items on word lists or learning to recognize new faces (Westrick et al. 1988; Mintzer and Griffiths 2002). As the dose increases, the resulting memory impairments tin become much more profound, sometimes culminating in blackouts—periods for which a person is unable to retrieve critical elements of events, or even entire events, that occurred while he or she was intoxicated.
Booze–Induced Blackouts
Blackouts represent episodes of amnesia, during which subjects are capable of participating even in salient, emotionally charged events—equally well as more mundane events—that they later cannot remember (Goodwin 1995). Like milder alcohol–induced retention impairments, these periods of amnesia are primarily "anterograde," significant that alcohol impairs the ability to form new memories while the person is intoxicated, simply does not typically erase memories formed earlier intoxication. Formal research into the nature of alcohol–induced blackouts began in the 1940s with the piece of work of E.M. Jellinek (1946). Jellinek'southward initial characterization of blackouts was based on data collected from a survey of Alcoholics Anonymous members. Noting that recovering alcoholics ofttimes reported having experienced alcohol–induced amnesia while they were drinking, Jellinek concluded that the occurrence of blackouts is a powerful indicator of alcoholism.
In 1969, Goodwin and colleagues published two of the most influential studies in the literature on blackouts (Goodwin et al. 1969a,b). Based on interviews with 100 hospitalized alcoholics, 64 of whom had a history of blackouts, the authors posited the existence of two qualitatively different types of blackouts: en bloc and fragmentary blackouts. People experiencing en bloc blackouts are unable to remember any details whatsoever from events that occurred while they were intoxicated, despite all efforts by the drinkers or others to cue recollect. Referring back to our general model of memory formation, it is every bit if the process of transferring information from short–term to long–term storage has been completely blocked. En bloc memory impairments tend to have a distinct onset. It is ordinarily less clear when these blackouts stop because people typically fall asleep before they are over. Interestingly, people appear able to go along information active in short–term retention for at least a few seconds. Every bit a event, they can often carry on conversations, drive automobiles, and appoint in other complicated behaviors. Information pertaining to these events is simply not transferred into long–term storage. Ryback (1970) wrote that intoxicated subjects in ane of his studies "could behave on conversations during the amnesic state, but could not remember what they said or did 5 minutes before. Their firsthand and remote memory were intact" (p. 1003). Similarly, in their report of memory impairments in intoxicated alcoholics, Goodwin and colleagues (1970) reported that subjects who experienced blackouts for testing sessions showed intact retentivity for up to two minutes while the sessions were taking identify.
Unlike en bloc blackouts, bitty blackouts involve fractional blocking of memory formation for events that occurred while the person was intoxicated. Goodwin and colleagues (1969a) reported that subjects experiencing fragmentary blackouts often become aware that they are missing pieces of events only subsequently beingness reminded that the events occurred. Interestingly, these reminders trigger at to the lowest degree some recall of the initially missing information. Research suggests that fragmentary blackouts are far more common than those of the en bloc variety (White et al. 2004; Hartzler and Fromme 2003b; Goodwin et al. 1969b).
Blackouts: State–Dependent Memory Germination?
Early anecdotal evidence suggested that blackouts might really reflect state–dependent information storage—that is, people might be able to remember events that occurred while they were intoxicated if they returned to that state (e.g., Goodwin et al. 1969a). State–dependent retention tin can exist viewed as a special case of a broader category known as context–dependent retentiveness (e.g., White et al. 2002a), in which cues that are associated with an result when a retentivity is formed tend to help trigger recall for that result at a later time. For instance, in a classic study by Godden and Baddeley (1975) defined who learned word lists either on land or under water remembered more than words when tested in the same context in which learning took place (i.e., land–land or h2o–water). Likewise, returning to the aforementioned emotional or physiological state that was nowadays when a memory was formed often can facilitate call back of that retentiveness. It is not uncommon to hear stories of drinkers who stash alcohol or money while intoxicated and can locate the hiding places only after condign intoxicated again (Goodwin 1995). Regardless of how compelling such stories can be, clear show of state–dependent learning under the influence of booze is lacking. In one recent study, Weissenborn and Duka (2000) examined whether subjects who learned give-and-take lists while intoxicated could recall more items if they were intoxicated again during the testing session. No such state–dependency was observed. Similarly, Lisman (1974) tried unsuccessfully to help subjects resurrect lost information for events occurring during periods of intoxication by getting them intoxicated one time once more.
Blood Alcohol Concentrations and Blackouts
Drinking large quantities of booze oftentimes precedes blackouts, simply several other factors also appear to play of import roles in causing such episodes of memory loss. Every bit Goodwin and colleagues (1969a) stated with regard to subjects in 1 of their studies, "Although blackouts almost always were associated with heavy drinking, this alone seemed insufficient to produce one. On many other occasions, subjects said they had boozer every bit much or more without memory loss" (p. 195). Amongst the factors that preceded blackouts were gulping drinks and drinking on an empty stomach, each of which leads to a rapid rise in BAC.
Subsequent inquiry provided additional bear witness suggesting a link between blackouts and quickly ascension BACs. Goodwin and colleagues (1970) examined the impact of astute alcohol exposure on memory formation in a laboratory setting. The author recruited 10 male subjects for the project, all but one through the unemployment office in St. Louis, Missouri. Almost subjects met diagnostic criteria for alcoholism and half had a history of frequent blackouts. The men were asked to eat roughly 16 to 18 ounces of 86–proof bourbon in approximately 4 hours. Kickoff one hour after subjects began drinking, memory was tested by presenting subjects with several different stimuli, including a series of children's toys and scenes from erotic films. Subjects were asked to recall details regarding these stimuli 2 minutes, 30 minutes, and 24 hours afterwards the stimuli were shown. Half of the subjects reported no recall for the stimuli or their presentation 30 minutes and 24 hours subsequently the events, though most seemed to call back the stimuli 2 minutes afterward presentation. Lack of recollect for the events 24 hours after, while sober, represents clear experimental evidence for the occurrence of blackouts. The fact that subjects could remember aspects of the events ii minutes afterward they occurred but not thirty minutes or 24 hours afterward provides compelling evidence that the blackouts stemmed from an inability to transfer information from brusk–term to long–term storage. For all only i subject in the blackout group, memory impairments began during the showtime few hours of drinking, when BAC levels were still ascension. The average peak BAC in this group, which was roughly 0.28 pct, occurred approximately 2.5 hours later on the onset of drinking.
In a similar study, Ryback (1970) examined the touch of booze on retentivity in seven hospitalized alcoholics given access to alcohol over the course of several days. All subjects were White males betwixt the ages of 31 and 44. Blackouts occurred in five of the seven subjects, as evidenced by an inability to think salient events that occurred while drinking the day before (e.g., one subject could not recall preparing to hit some other over the head with a chair). Estimates of BAC levels during blackout periods suggested that they frequently began at levels around 0.20 percent and as low as 0.14 percent. The duration of blackouts ranged from nine hours to iii days. Based on his observations, Ryback concluded that a central predictor of blackouts was the rate at which subjects consumed their drinks. He stated, "Information technology is important to notation that all the blackout periods occurred afterward a rapid rise in blood booze level" (p. 622). The two subjects who did not blackness out, despite becoming extremely intoxicated, experienced irksome increases in blood booze levels.
Blackouts Amidst Social Drinkers
Most of the inquiry conducted on blackouts during the past fifty years has involved surveys, interviews, and direct ascertainment of middle–anile, primarily male alcoholics, many of whom were hospitalized. Researchers have largely ignored the occurrence of blackouts amidst immature social drinkers, and so the idea that blackouts are an unlikely consequence of heavy drinking in nonalcoholics has remained deeply entrenched in both the scientific and pop cultures. Yet at that place is clear evidence that blackouts do occur among social drinkers. Knight and colleagues (1999) observed that 35 percent of trainees in a large pediatric residency program had experienced at least one coma. Similarly, Goodwin (1995) reported that 33 pct of the first–year medical students he interviewed acknowledged having had at least one blackout. "They were inexperienced," he wrote. "They drank likewise much too quickly, their blood levels rose extremely speedily, and they experienced amnesia" (p. 315). In a study of 2,076 Finnish males, Poikolainen (1982) found that 35 percent of all males surveyed had had at least one blackout in the year before the survey.
As might be expected given the excessive drinking habits of many college students (Wechsler et al. 2002), this population normally experiences blackouts. White and colleagues (2002c) recently surveyed 772 undergraduates regarding their experiences with blackouts. Respondents who answered aye to the question "Have you always awoken after a nighttime of drinking not able to remember things that you lot did or places that you went?" were considered to have experienced blackouts. Fifty–one percent of the students who had ever consumed alcohol reported blacking out at some point in their lives, and 40 percent reported experiencing a blackout in the year earlier the survey. Of those who had consumed alcohol during the 2 weeks earlier the survey, nine.4 percent reported blacking out during this menstruum. Students in the study reported that they later learned that they had participated in a wide range of events they did non remember, including such meaning activities as vandalism, unprotected intercourse, driving an automobile, and spending money.
During the two weeks preceding the survey, an equal percentage of males and females experienced blackouts, despite the fact that males drank significantly more often and more heavily than females. This event suggests that at any given level of alcohol consumption, females—a group infrequently studied in the literature on blackouts—are at greater risk than males for experiencing blackouts. The greater tendency of females to blackness out likely arises, in part, from well–known gender differences in physiological factors that affect alcohol distribution and metabolism, such every bit body weight, proportion of body fatty, and levels of key enzymes. There also is some testify that females are more than susceptible than males to milder forms of alcohol–induced retention impairments, fifty-fifty when given comparable doses of booze (Mumenthaler et al. 1999).
In a subsequent report, White and colleagues (2004) interviewed 50 undergraduate students, all of whom had experienced at to the lowest degree 1 blackout, to gather more information near the factors related to blackouts. As in the previous study, students reported engaging in a range of risky behaviors during blackouts, including sexual activity with both acquaintances and strangers, vandalism, getting into arguments and fights, and others. During the night of their virtually recent blackout, most students drank either liquor lone or in combination with beer. Simply 1 student out of 50 reported that the most recent coma occurred after drinking beer alone. On boilerplate, students estimated that they consumed roughly 11.5 drinks before the onset of the coma. Males reported drinking significantly more than than females, but they did and so over a significantly longer period of fourth dimension. As a result, estimated summit BACs during the nighttime of the terminal blackout were similar for males (0.30 percent) and females (0.35 pct). Equally Goodwin observed in his work with alcoholics (1969b), fragmentary blackouts occurred far more often than en bloc blackouts, with four out of 5 students indicating that they eventually recalled bits and pieces of the events. Roughly half of all students (52 pct) indicated that their first full retentiveness after the onset of the blackout was of waking upwardly in the forenoon, frequently in an unfamiliar location. Many students, more females (59 pct) than males (25 percentage), were frightened by their last blackout and changed their drinking habits as a issue.
Use of Other Drugs During Blackouts
Booze interacts with several other drugs, many of which are capable of producing amnesia on their own. For example, diazepam (Valium®) and flunitrazepam (Rohypnol) are benzodiazepine sedatives that can produce severe memory impairments at high doses (White et al. 1997; Saum and Inciardia 1997). Alcohol enhances the effects of benzodiazepines (for a review, see Silvers et al. 2003). Thus, combining these compounds with alcohol could dramatically increase the likelihood of experiencing memory impairments. Similarly, the combination of booze and THC, the chief psychoactive chemical compound in marijuana, produces greater memory impairments than when either drug is given alone (Ciccocioppo et al. 2002). Given that many college students use other drugs in combination with alcohol (O'Malley and Johnston 2002), some of the blackouts reported past students may ascend from polysubstance use rather than from alcohol alone. Indeed, based on interviews with 136 heavy–drinking immature adults (mean historic period 22), Hartzler and Fromme (2003b) concluded that en bloc blackouts often ascend from the combined use of alcohol and other drugs. White and colleagues (2004) observed that, among fifty undergraduate students with a history of blackouts, merely 3 students reported using other drugs during the nighttime of their nearly recent blackout, and marijuana was the drug in each case.
Are Some People More than Likely Than Others to Experience Blackouts?
In classic studies of hospitalized alcoholics by Goodwin and colleagues (1969a,b), 36 out of the 100 patients interviewed indicated that they had never experienced a blackout. In some ways, the patients who did not experience blackouts are as interesting equally the patients who did. What was it virtually these 36 patients that kept them from blacking out, despite the fact that their alcoholism was and then severe that it required hospitalization? Although they may actually have experienced blackouts only but were unaware of them, at that place may take been something fundamentally different about these patients that diminished their likelihood of experiencing memory impairments while drinking.
In support of this possibility, a recent study by Hartzler and Fromme (2003a) suggests that people with a history of blackouts are more than vulnerable to the effects of booze on memory than those without a history of blackouts. These authors recruited 108 college students, one-half of whom had experienced at least 1 bitty coma in the previous year. While sober, members of the two groups performed comparably in memory tasks. However, when they were mildly intoxicated (0.08 pct BAC) those with a history of bitty blackouts performed worse than those without such a history. There are 2 possible interpretations for these data, both of which support the hypothesis that some people are more susceptible to blackouts than others. 1 plausible interpretation is that subjects in the fragmentary blackout group always have been more vulnerable to booze–induced memory impairments, which is why they performed poorly during testing nether booze, and why they are members of the blackout grouping in the first identify. A second interpretation is that subjects in the blackout group performed poorly during testing as a result of drinking enough in the past to experience booze–induced memory impairments. In other words, mayhap their prior exposure to alcohol damaged the brain in a way that predisposed them to experiencing future retention impairments. This latter possibility is made more likely past recent testify that students who engage in repeated episodes of heavy, or rampage, drinking are more likely than other students to exhibit retentivity impairments when they are intoxicated (Weissenborn and Duka 2000). Similar results have been observed in fauna studies (White et al. 2000a).
The argument for an inherent vulnerability to alcohol–induced memory impairments, including blackouts, is strengthened past ii contempo studies. In an impressive longitudinal study, Baer and colleagues (2003) examined the drinking habits of pregnant women in 1974 and 1975, and and so studied booze utilise and related problems in their offspring at vii dissimilar fourth dimension points during the following 21 years. These authors observed that prenatal alcohol exposure was associated with increased rates of experiencing alcohol–related consequences, including blackouts, even after controlling for the offsprings' general drinking habits. In add-on, a recent report by Nelson and colleagues (2004) suggests that there might actually exist a genetic contribution to the susceptibility to blackouts, indicating that some people simply are built in a way that makes them more than vulnerable to alcohol–induced amnesia.
Every bit discussed in the section below on the potential encephalon mechanisms underlying booze–induced amnesia, information technology is like shooting fish in a barrel to imagine that the impact of alcohol on brain circuitry could vary from person to person, rendering some people more sensitive than others to the memory–impairing effects of the drug.
HOW DOES Alcohol IMPAIR MEMORY?
During the first half of the 20th century, two theoretical hurdles hampered progress toward an agreement of the mechanisms underlying the furnishings of booze on retentivity. More contempo research has cleared away these hurdles, allowing for tremendous gains in the area during the by 50 years.
The starting time hurdle concerned scientists' understanding of the functional neuroanatomy of memory. In the 1950s, following observations of an amnesic patient known as H.One thousand., it became clear that different encephalon regions are involved in the formation, storage, and retrieval of different types of retention. In 1953, large portions of H.M.'due south medial temporal lobes, including most of his hippocampus, were removed in an endeavor to command intractable seizures (Scoville and Milner 1957). Although the frequency and severity of H.G.'s seizures were significantly reduced by the surgery, it soon became clear that H.M. suffered from a dramatic syndrome of retention impairments. He still was able to acquire basic motor skills, keep information active in short–term memory for a few seconds or more than if left undistracted, and recollect episodes of his life from long ago, just he was unable to form new long–term memories for facts and events. The pattern of H.1000.'s impairments too forced a re–exam of models of long–term memory storage. Specifically, although H.Thou. was able to retrieve long–term memories formed roughly a yr or more than before his surgery, he could not remember events that transpired within the yr preceding his surgery. This strongly suggests that the transfer of data into long–term storage actually takes place over several years, with the hippocampus being necessary for its retrieval for the offset year or so.
Subsequent research with other patients confirmed that the hippocampus, an irregularly shaped structure deep in the forebrain, is critically involved in the formation of memories for events (come across effigy 2 for a depiction of the brain, with the hippocampus and other relevant structures highlighted). Patient R.B. lost a significant corporeality of claret as a result of middle surgery. He survived simply showed retentiveness impairments similar to those exhibited by H.M. Upon his death, histology revealed that the loss of claret to R.B.'s encephalon damaged a small-scale region of the hippocampus called hippocampal expanse CA1, which contains neurons known as pyramidal cells because of the triangular shape of their prison cell bodies (Zola–Morgan et al. 1986). Hippocampal CA1 pyramidal cells assist the hippocampus in communicating with other areas of the brain. The hippocampus receives information from a wide diversity of encephalon regions, many of them located in the tissue, called the neocortex, that blankets the encephalon and surrounds other brain structures. (Neocortex literally ways "new bawl" or "new covering." When ane looks at a picture of the human brain, nearly of what is visible is neocortex.) The hippocampus somehow ties data from other encephalon regions together to course new autobiographical memories, and CA1 pyramidal cells send the results of this processing back out to the neocortex. As is articulate from patient R.B., removing CA1 pyramidal cells from the circuitry prevents the hippocampal memory arrangement from doing its task.
Figure 2 The man brain, showing the location of the hippocampus, the frontal lobes, and the medial septum.
The second barrier to understanding the mechanisms underlying booze's effects on retention was an incomplete understanding of how alcohol affects brain function at a cellular level. Until recently, alcohol was causeless to affect the encephalon in a general way, merely shutting downward the action of all cells with which it came in contact. The pervasiveness of this assumption is reflected in numerous writings during the early on 20th century. For instance, Fleming (1935) wrote, "The prophetic generalization of Schmiedeberg in 1833 that the pharmacological action of alcohol on the cerebrum is purely depressant has been constitute, most pharmacologists volition concord, to characterize its action in general on all tissues" (p. 89). During the 1970s, researchers hypothesized that alcohol depressed neural action by altering the motility of key molecules (in item, lipids) in nerve cell membranes. This change and so led to alterations in the action of proteins, including those that influence communication between neurons past controlling the passage of positively or negatively charged atoms (i.e., ions) through cell membranes (e.k., Chin and Goldstein 1977). This view persisted into the tardily 1980s, at which time the consensus began to shift as evidence mounted that booze has selective furnishings on the brain's nerve–jail cell advice (i.e., neurotransmitter) systems, altering activity in some types of receptors but not others (e.yard., Criswell et al. 1993). Substantial bear witness at present indicates that alcohol selectively alters the activity of specific complexes of proteins embedded in the membranes of cells (i.eastward., receptors) that bind neurotransmitters such as gamma–aminobutyric acid (GABA), glutamate, serotonin, acetylcholine, and glycine (for a review, see Little 1999). In some cases, only a few amino acids appear to distinguish receptors that are sensitive to alcohol from those that are not (Peoples and Stewart 2000). It remains unclear exactly how alcohol interacts with receptors to alter their activity.
Alcohol, Memory, and the Hippocampus
More than than 30 years agone, both Ryback (1970) and Goodwin and colleagues (1969a) speculated that alcohol might impair memory germination by disrupting activity in the hippocampus. This speculation was based on the observation that acute alcohol exposure (in humans) produces a syndrome of retention impairments like in many means to the impairments produced by hippocampal damage. Specifically, both astute alcohol exposure and hippocampal damage impair the ability to class new long–term, explicit memories but practise not touch on curt–term retentivity storage or, in full general, the recall of information from long–term storage.
Research conducted in the past few decades using animal models supports the hypothesis that alcohol impairs memory germination, at least in role, by disrupting action in the hippocampus (for a review, see White et al. 2000b). Such enquiry has included behavioral observation; examination of slices of and brain tissue, neurons in cell civilisation, and brain activity in anesthetized or freely behaving animals; and a multifariousness of pharmacological techniques.
As mentioned above, damage limited to the CA1 region of the hippocampus dramatically disrupts the ability to form new explicit memories (Zola–Morgan et al. 1986). In rodents, the actions of CA1 pyramidal cells have striking behavioral correlates. Some cells tend to discharge electrical signals that result in one cell communicating with other cells (i.e., action potentials) when the rodent is in a singled-out location in its surround. The location differs for each jail cell. For instance, while a rat searches for food on a plus–shaped maze, ane pyramidal cell might generate action potentials primarily when the rat is at the far end of the north arm, while another might generate action potentials primarily when the rat is in the middle of the south arm, and so on. Collectively, the cells that are active in that particular environment create a spatial, or contextual map that serves as a framework for event memories created in that environment. Because of the location–specific firing of these cells, they ofttimes are referred to equally "place–cells," and the regions of the environment in which they burn are referred to as "place–fields" (for reviews, encounter Best and White 1998; Best et al. 2001). Given that CA1 pyramidal cells are critically important to the formation of memories for facts and events, and the clear behavioral correlates of their activity in rodents, information technology is possible to assess the impact of alcohol on hippocampal output in an intact, fully functional brain by studying these cells.
In recent work with awake, freely behaving rats, White and Best (2000) showed that alcohol profoundly suppresses the activity of pyramidal cells in region CA1. The researchers immune the rats to provender for food for xv minutes in a symmetric, Y–shaped maze and measured the animals' hippocampal action using tiny wires (i.e., microelectrodes) implanted in their brains. Effigy 3 displays the activity of an individual CA1 pyramidal cell. The activity—which corresponds to the middle portion of the lower left arm of the maze—is shown before alcohol administration (A), 45 to hour subsequently booze administration (B), and 7 hours after alcohol assistants (C). The dose of booze used in the testing session was 1.5 grams per kilogram of body weight—enough to produce a summit BAC of about 0.16 percent. (A corresponding BAC in humans would be twice the legal driving limit in almost States.) Equally the figure illustrates, the cell'southward action was essentially shut off by alcohol. Neural activity returned to near–normal levels within near seven hours of alcohol administration.
Figure three Booze suppresses hippocampal pyramidal cell activity in an awake, freely behaving rat. Pyramidal cells oft fire when the beast is in discrete regions of its environment, earning them the title "place–cells." The specific areas of the environment where these cells burn down are referred to as identify–fields. The effigy shows the activity of an individual pyramidal cell earlier alcohol administration (baseline), 45 to lx minutes after alcohol administration, and seven hours after alcohol assistants (one.5 g/kg). Each frame in the figure shows the firing rate and firing location of the cell across a xv–minute block of time during which the rat was foraging for food on a symmetric, Y–shaped maze. White pixels are pixels in which the cell fired at very depression rates, and darker colors represent higher firing rates (see cardinal to the correct of figure). Equally is clear from a comparison of activity during baseline and 45 to sixty minutes afterwards alcohol administration, the activeness of the jail cell was essentially shut off by alcohol. Neural activity returned to near normal levels within roughly 7 hours after alcohol administration.
White and Best administered several doses of alcohol in this report, ranging from 0.five g/kg to 1.5 thousand/kg. (Only ane of the experiments is represented in figure 3.) They establish that the dose affected the degree of pyramidal prison cell suppression. Although 0.5 thou/kg did not produce a pregnant modify in the firing of hippocampal pyramidal cells, ane.0 and 1.v k/kg produced significant suppression of firing during a one–hour testing session following alcohol assistants. The dose–dependent suppression of CA1 pyramidal cells is consistent with the dose–dependent effects of alcohol on episodic memory formation.
Alcohol and Hippocampal Long–Term Potentiation
In add-on to suppressing the output from pyramidal cells, booze has several other furnishings on hippocampal function. For instance, booze severely disrupts the power of neurons to establish long–lasting, heightened responsiveness to signals from other cells (Bliss and Collinridge 1993). This heightened responsiveness is known equally long–term potentiation (LTP). Because researchers have theorized that something like LTP occurs naturally in the brain during learning (for a review, see Martin and Morris 2002), many investigators have used LTP as a model for studying the neurobiology underlying the effects of drugs, including alcohol, on retentivity.
In a typical LTP experiment, two electrodes (A and B) are lowered into a piece of hippocampal tissue kept alive by bathing information technology in oxygenated bogus cerebral spinal fluid (ACSF). A small amount of current is passed through electrode A, causing the neurons in this area to send signals to cells located almost electrode B. Electrode B then is used to record how the cells in the area respond to the incoming signals. This response is the baseline response. Next, a specific pattern of stimulation intended to model the pattern of activity that might occur during an actual learning event is delivered through electrode A. When the original stimulus that elicited the baseline response is delivered again through electrode A, the response recorded at electrode B is larger (i.e., potentiated). In other words, every bit a consequence of the patterned input, cells at position B at present are more than responsive to signals sent from cells at position A. The potentiated response often lasts for an extended period of time, hence the term long–term potentiation.
Booze interferes with the establishment of LTP (Morrisett and Swartzwelder 1993; Givens and McMahon 1995; Pyapali et al. 1999; Schummers and Browning 2001), and this impairment begins at concentrations equivalent to those produced by consuming simply one or ii standard drinks (due east.grand., a 12–oz beer, i.5–oz of liquor in a shot or mixed drink, or a 5–oz glass of wine) (Blitzer et al. 1990). If sufficient alcohol is present in the ACSF bathing the slice of hippocampal tissue when the patterned stimulation is given, the response recorded afterward at position B will not exist larger than it was at baseline (that is, information technology volition not be potentiated). And, just equally alcohol tends non to impair remember of memories established before alcohol exposure, alcohol does not disrupt the expression of LTP established before alcohol exposure.
Ane of the fundamental requirements for the establishment of LTP in the hippocampus is that a type of betoken receptor known every bit the NMDA2 receptor becomes activated. (2 Due north–methyl–D–aspartate [NMDA] is a receptor for the neurotransmitter glutamate.) Activation of the NMDA receptor allows calcium to enter the prison cell, which sets off a chain of events leading to long–lasting changes in the cell's construction or function, or both. Alcohol interferes with the activation of the NMDA receptor, thereby preventing the influx of calcium and the changes that follow (Swartzwelder et al. 1995). This is believed to exist the primary mechanism underlying the effects of booze on LTP, though other transmitter systems probably are also involved (Schummers and Browning 2001).
Indirect Effects of Alcohol on Hippocampal Function
Like other brain regions, the hippocampus does non operate in isolation. Information processing in the hippocampus depends on coordinated input from a diversity of other structures, which gives alcohol and other drugs additional opportunities to disrupt hippocampal functioning. Ane encephalon region that is central to hippocampal functioning is a small structure in the fore brain known every bit the medial septum (Givens et al. 2000). The medial septum sends rhythmic excitatory and inhibitory signals to the hippocampus, causing rhythmic changes in the activity of hippocampal pyramidal cells. In electroencephalograph recordings, this rhythmic action, referred to as the theta rhythm, occurs within a frequency of roughly half dozen to 9 cycles per second (hertz) in actively behaving rats. The theta rhythm is idea to act as a gatekeeper, increasing or decreasing the likelihood that information entering the hippocampus from cortical structures will be processed (Orr et al. 2001). (For more data on the role of electrophysiology in diagnosing alcohol problems, see the article in this issue by Porjesz and Begleiter.) Data inbound the hippocampus when pyramidal cells are slightly excited (i.e., slightly depolarized) has a better adventure of influencing hippocampal circuitry than signals that get in when the cells are slightly suppressed (i.e., slightly hyperpolarized).
Manipulations that disrupt the theta rhythm also disrupt the ability to perform tasks that depend on the hippocampus (Givens et al. 2000). Alcohol disrupts the theta rhythm in large part past suppressing the output of signals from medial septal neurons to the hippocampus (Steffensen et al. 1993; Givens et al. 2000). Given the powerful influence that the medial septum has on information processing in the hippocampus, the impact of alcohol on cellular activeness in the medial septum is likely to play an important role in the effects of alcohol on memory. Indeed, in rats, putting alcohol straight into the medial septum alone produces memory impairments (Givens and McMahon 1997).
Other Brain Regions Involved in Alcohol–Induced Retentivity Impairments
The hippocampus is non the only structure involved in retentiveness formation. A host of other brain structures as well are involved in memory germination, storage, and retrieval (Eichenbaum 2002). Recent research with humans has yielded compelling evidence that key areas of the frontal lobes play important roles in curt–term retentiveness and the formation and retrieval of long–term explicit memories (e.g., Shastri 2002; Curtis and D'Esposito 2003; Ranganath et al. 2003). Harm to the frontal lobes leads to profound cognitive impairments, one of which is a difficulty forming new memories. Recent evidence suggests that memory processes in the frontal lobes and the hippocampus are coordinated via reciprocal connections (Wall and Messier 2001; Shastri 2002), raising the possibility that dysfunction in one construction could take deleterious effects on the functioning of the other.
Considerable evidence suggests that chronic alcohol apply damages the frontal lobes and leads to impaired performance of tasks that rely on frontal lobe functioning (Kril and Halliday 1999; Moselhy et al. 2001). "Shrinkage" in brain volume, changes in gene expression, and disruptions in how performing certain tasks affects blood catamenia in the brain all have been observed in the frontal lobes of booze–dependent subjects (Kril and Halliday 1999; Lewohl et al. 2000; Tapert et al. 2001; Kubota et al. 2001; Desmond et al. 2003).
Although much is known about the effects of chronic (i.e., repeated) use of alcohol on frontal lobe function, little is known about the effects of ane–fourth dimension (i.e., astute) utilize of alcohol on activity in the frontal lobes, or the relationship of such effects to alcohol–induced retentivity impairments. Compelling evidence indicates that acute alcohol use impairs the performance of a multifariousness of frontal lobe–mediated tasks, like those that crave planning, decisionmaking, and impulse control (Weissenborn and Duka 2003; Burian et al. 2003), but the underlying mechanisms are non known. Research also suggests that baseline blood flow to the frontal lobes increases during acute intoxication (Volkow et al. 1988; Tiihonen et al. 1994), that metabolism in the frontal lobes decreases (Wang et al. 2000), and that alcohol reduces the amount of activity that occurs in the frontal lobes when the frontal lobes are exposed to pulses from a strong magnetic field (Kahkonen et al. 2003). Although the exact meaning of these changes remains unclear, the evidence suggests that acute intoxication alters the normal functioning of the frontal lobes. Futurity inquiry is needed to shed more light on this important question. In particular, research in animals will be an important supplement to studies in humans, affording a better understanding of the underlying prefrontal circuitry involved in alcohol–induced retentivity impairment.
SUMMARY AND CONCLUSIONS
As detailed in this cursory review, booze can take a dramatic impact on retention. Alcohol primarily disrupts the ability to class new long–term memories; information technology causes less disruption of retrieve of previously established long–term memories or of the ability to keep new information active in brusque–term memory for a few seconds or more. At low doses, the impairments produced by booze are often subtle, though they are detectable in controlled conditions. As the amount of alcohol consumed increases, so does the magnitude of the memory impairments. Large quantities of alcohol, peculiarly if consumed quickly, can produce a blackout, an interval of time for which the intoxicated person cannot recall key details of events, or even entire events. En bloc blackouts are stretches of time for which the person has no memory whatsoever. Fragmentary blackouts are episodes for which the drinker'southward memory is spotty, with "islands" of memory providing some insight into what transpired, and for which more recall ordinarily is possible if the drinker is cued by others. Blackouts are much more common amidst social drinkers than previously causeless and should exist viewed as a potential upshot of acute intoxication regardless of age or whether one is clinically dependent upon alcohol.
Tremendous progress has been made toward an agreement of the mechanisms underlying alcohol–induced memory impairments. Alcohol disrupts action in the hippocampus via several routes—directly, through furnishings on hippocampal circuitry, and indirectly, by interfering with interactions between the hippocampus and other encephalon regions. The affect of alcohol on the frontal lobes remains poorly understood, simply probably plays an important function in booze–induced retentivity impairments.
Modern neuroimaging techniques, such equally positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provide incredible opportunities for investigating the touch of drugs like alcohol on encephalon function during the performance of cognitive tasks. The use of these techniques will no doubt yield of import data regarding the mechanisms underlying alcohol–induced memory impairments in the coming years. Memory formation and retrieval are highly influenced by factors such as attention and motivation (e.g., Kensinger et al. 2003). With the assistance of neuroimaging techniques, researchers may exist able to examine the impact of booze on brain activity related to these factors, and and so make up one's mind how alcohol contributes to retentivity impairments.
Despite advances in human neuroimaging techniques, beast models remain admittedly essential in the written report of mechanisms underlying alcohol–induced memory impairments. Hopefully, future work volition reveal more than regarding the means in which the furnishings of alcohol on multiple transmitter systems interact to disrupt memory formation. Similarly, recent advances in electrophysiological recording techniques, which allow for recordings from hundreds of individual cells in several brain regions simultaneously (Kralik et al. 2001), could provide much–needed information regarding the touch on of alcohol on the interactions between disparate brain regions involved in the encoding, storage, and retrieval of information.
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