Alcohol-related Memories Research Articles

Trying to forget alcohol: Brain mechanisms underlying memory suppression in young binge drinkers

People are able to voluntarily suppress unwanted thoughts or memories, a phenomenon known as suppression-induced forgetting or memory suppression. Despite harmful alcohol use, such as binge drinking, has been linked to impaired inhibitory control (IC) and augmented alcohol-cue reactivity, no study to date has assessed memory inhibition abilities towards alcohol-related cues in binge drinkers (BDs). Thus, the present preregistered study aimed to evaluate the behavioral and neurofunctional mechanisms associated with memory inhibition, specifically those related to the suppression of alcohol-related memories, in young BDs. For this purpose, electroencephalographic activity was recorded in eighty-two college students aged between 18 and 24 years old from the University of Minho (50% females; 40 non/low-drinkers [N/LDS] and 42 BDs) while they performed the Think/No-Think Alcohol task. Brain functional connectivity (FC) was calculated using the phase locking value and, subsequently, a dynamic seed-based analysis was conducted to explore the FC patterns between IC and memory networks. Comparatively to N/LDs, BDs exhibited decreased alpha-band FC between the anterior cingulate cortex and the left fusiform gyrus during attempts to suppress non-alcohol memories, accompanied by unsuccessful forgetting of those memories. Conversely, BDs displayed augmented gamma-band FC between the IC network and memory regions –i.e., hippocampus, parahippocampus and fusiform gyrus- during suppression of alcohol-related memories. Inhibitory abnormalities in BDs may lead to hypoconnectivity between IC and memory networks and deficient suppression of non-alcohol-related memories. However, while suppressing highly salient and reward-predicting stimuli, such as alcohol-related memories, BDs display a hyperconnectivity pattern between IC and memory networks, likely due to their augmented attention towards intrusive alcoholic memories and the attempts to compensate for potential underlying IC deficits. These findings hold important implications for alcohol research and treatment, as they open up new avenues for reducing alcohol use by shifting the focus to empowering suppression/control over alcohol-related memories. Clinical trial registration[http://www.ClinicalTrials.gov], identifier [NCT05237414].

Lateral hypothalamic GABAergic neurons encode alcohol memories

In alcohol use disorder, the alcohol memories persist during abstinence, and exposure to stimuli associated with alcohol use can lead to relapse. This highlights the importance of investigating the neural substrates underlying not only relapse but also encoding and expression of alcohol memories. GABAergic neurons in the lateral hypothalamus (LH-GABA) have been shown to be critical for food-cue memories and motivation; however, the extent to which this role extends to alcohol-cue memories and motivations remains unexplored. In this study, we aimed to describe how alcohol-related memories are encoded and expressed in LH GABAergic neurons. Our first step was to monitor LH-GABA calcium transients during acquisition, extinction, and reinstatement of an alcohol-cue memory using fiber photometry. We trained the rats on a Pavlovian conditioning task, where one conditioned stimulus (CS+) predicted alcohol (20% EtOH) and another conditioned stimulus (CS-) had no outcome. We then extinguished this association through non-reinforced presentations of the CS+ and CS- and finally, in two different groups, we measured relapse under non-primed and alcohol-primed induced reinstatement. Our results show that initially both cues caused increased LH-GABA activity, and after learning only the alcohol cue increased LH-GABA activity. After extinction, this activity decreases, and we found no differences in LH-GABA activity during reinstatement in either group. Next, we inhibited LH-GABA neurons with optogenetics to show that activity of these neurons is necessary for the formation of an alcohol-cue association. These findings suggest that LH-GABA might be involved in attentional processes modulated by learning.

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.

For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking. Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory. Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking. Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.

New Approaches for Alcohol Use Disorder Treatment via Memory Retrieval and Reconsolidation Manipulations.

Relapse to alcohol seeking and drinking is a major clinical challenge in alcohol use disorder and is frequently brought about by cue-induced craving, caused by exposure to cues that evoke alcohol-related memories. It has been postulated that memories become labile for manipulation shortly after their retrieval and then restabilize in a "memory reconsolidation" process. Disruption or interference with the reconsolidation of drug-associated memories has been suggested as a possible strategy to reduce or even prevent cue-induced craving and relapse. Here, we review literature demonstrating the capacity of behavioral or pharmacological manipulations to reduce relapse in animal models and humans when applied after a short retrieval of memories associated with alcohol, suggestively disrupting the reconsolidation of such memories. We suggest that while there is a clear potential of using post-retrieval manipulations to target specific relapse-evoking memories, future research should be more systematic, standardized, and translational. Specifically, we discuss several critical limitations and boundary conditions, which should be addressed to improve consistency and replicability in the field and lead to the development of an efficient reconsolidation-based relapse prevention therapy.

Forgetting Alcohol: A Double-Blind, Randomized Controlled Trial Investigating Memory Inhibition Training in Young Binge Drinkers.

BackgroundBinge Drinking (BD) has been associated with altered inhibitory control and augmented alcohol-cue reactivity. Memory inhibition (MI), the ability to voluntarily suppress unwanted thoughts/memories, may lead to forgetting of memories in several psychiatric conditions. However, despite its potential clinical implications, no study to date has explored the MI abilities in populations with substance misuse, such as binge drinkers (BDs).MethodThis study—registered in the NIH Clinical Trials Database (ClinicalTrials.gov identifier: NCT05237414)—aims firstly to examine the behavioral and electroencephalographic (EEG) correlates of MI among college BDs. For this purpose, 45 BDs and 45 age-matched non/low-drinkers (50% female) will be assessed by EEG while performing the Think/No-Think Alcohol task, a paradigm that evaluates alcohol-related MI. Additionally, this work aims to evaluate an alcohol-specific MI intervention protocol using cognitive training (CT) and transcranial direct current stimulation (tDCS) while its effects on behavioral and EEG outcomes are assessed. BDs will be randomly assigned to one MI training group: combined [CT and verum tDCS applied over the right dorsolateral prefrontal cortex (DLPFC)], cognitive (CT and sham tDCS), or control (sham CT and sham tDCS). Training will occur in three consecutive days, in three sessions. MI will be re-assessed in BDs through a post-training EEG assessment. Alcohol use and craving will be measured at the first EEG assessment, and both 10-days and 3-months post-training. In addition, behavioral and EEG data will be collected during the performance of an alcohol cue reactivity (ACR) task, which evaluates attentional bias toward alcoholic stimuli, before, and after the MI training sessions.DiscussionThis study protocol will provide the first behavioral and neurofunctional MI assessment in BDs. Along with poor MI abilities, BDs are expected to show alterations in event-related potentials and functional connectivity patterns associated with MI. Results should also demonstrate the effectiveness of the protocol, with BDs exhibiting an improved capacity to suppress alcohol-related memories after both combined and cognitive training, along with a reduction in alcohol use and craving in the short/medium-term. Collectively, these findings might have major implications for the understanding and treatment of alcohol misuse.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT05237414].

Brain functional connectivity after cognitive-bias modification and behavioral changes in abstinent alcohol-use disorder patients

The use of the cognitive-bias modification (CBM) method has emerged as a therapeutic complement in the treatment of alcoholism, producing changes at behavioral and brain level. Nevertheless, the impact of the CBM procedure could be improved by the memory retrieval-extinction process (REP). Different studies have demonstrated that the retrieval of drug memories before extinction training later reduced the reinstatement of drug-seeking behavior. The main aim of this work was to study the effect of the CBM procedure itself, as well as in combination with the activation of alcohol-related memories, on the brain oscillatory activity of abstinent patients with alcohol-use disorder. The study sample comprised 33 patients divided into three groups: A-CBM (alcohol-related memory activation + CBM), N-CBM (neutral memory activation + CBM) and N-INT (no-intervention) groups. A resting-state EEG was obtained before and after each protocol, along with the assessment of the automatic action tendencies. A-CBM group showed a general alpha synchronization increase after the protocol, while the other groups did not show any significant change. Besides, A-CBM group showed significant intra and inter-group differences in the automatic action tendencies after the protocol, reflected in higher avoidance bias toward appetitive, aversive and without context alcohol-related stimuli. The alpha phase synchronization increase could be the neural manifestation of the conditioning produced between the alcohol-related stimuli and the automatic avoidance response. Moreover, the activation of the alcohol-related memories favors this conditioning with those alcohol-related stimuli associated with the activated memories, because it increases their threat level for the abstinence maintenance.

The Think/No-Think Alcohol Task: A New Paradigm for Assessing Memory Suppression in Alcohol-Related Contexts.

Research with the Think/No-Think (TNT) task has shown that voluntary suppression of an unwanted memory may lead to its later forgetting. To date, however, no study has assessed the memory suppression abilities in alcohol-related contexts despite the potential implications that it might have for alcohol research. With this aim, we developed a new version of the TNT paradigm, the TNT Alcohol (TNTA) task, which consists of 36 neutral pictures paired with 36 alcohol/no-alcohol images that are instructed to be suppressed or recollected. Electroencephalographic activity was recorded from 64 electrodes while 20 young healthy females performed the TNTA task. The event-related potentials (ERPs) typically involved in memory suppression/recollection were analyzed, namely the fronto-central N2, the late parietal positivity (LPP), and the frontal slow wave (FSW). Findings revealed reduced recall for previously learned images that were subsequently instructed to be suppressed (No-Think) relative to those instructed to be retrieved (Think) and those not cued to be suppressed or retrieved (Baseline). This reduction seemed to be more prominent for alcohol-related memories. In addition, ERP analysis showed that compared to attempts of recollection, attempts of memory suppression were associated with attenuated LPP amplitude-more pronounced for alcohol-related memories-(indicating reduced conscious recollection for No-Think images) as well as with increased FSW (suggesting strategic control aiming at decrease accessibility of unwanted memories). These results replicate and extend previously reported behavioral and ERP findings in the TNT paradigm and suggest that the TNTA task may be a useful instrument to measure the ability to suppress alcohol-related memories.

Mood Induction Changes Negative Alcohol Expectancies Among Japanese Adults with Problematic Drinking: Negative Mood Regulation Expectancies Moderate the Effect

One’s beliefs about effects of alcohol, known as alcohol expectancies, are important constructs for understanding drinking behavior, but the literature on the influences of mood on alcohol-related negative beliefs and on memory accessibility is limited. The current study examined effects of a mood induction on alcohol expectancies and alcohol-related autobiographical memories; also, whether negative mood regulation expectancies (NMRE), which are beliefs about one’s ability to control negative affect, moderated these effects. Recruited from the community, 485 Japanese problem drinkers first completed measures of NMRE and alcohol expectancies. A week later, participants completed an online experiment: they received a musical mood induction (238 participants were randomly allocated to a positive mood induction group and 239 participants to a negative mood induction group). Then, participants completed measures of alcohol expectancies and alcohol-related autobiographical memories. Results showed the mood induction significantly weakly affected two negative alcohol expectancies (physical ailments and dysphoria). NMRE moderated the effect of mood induction on negative alcohol expectancies for dysphoria. Findings suggest the importance of mood as an influence on negative beliefs about the effects of drinking among Japanese problem drinkers. Additionally, NMRE alter the impact of mood on more specific expectancies. Limitations about the online method of this experiment are discussed.

Commentary: Rewriting the Valuation and Salience of Alcohol-Related Stimuli via Memory Reconsolidation

Commentary: Rewriting the Valuation and Salience of Alcohol-Related Stimuli via Memory Reconsolidation

MTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors

Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels. Furthermore, we demonstrate that alcohol intake also blocks glycogen synthase kinase-3β (GSK-3β)-phosphorylation of CRMP-2, which results in elevated binding of CRMP-2 to microtubules and a concomitant increase in microtubule content. Finally, we show that systemic administration of the CRMP-2 inhibitor lacosamide, or knockdown of CRMP-2 in the NAc decreases excessive alcohol intake. These results suggest that CRMP-2 in the NAc is a convergent point that receives inputs from two signaling pathways, mTORC1 and GSK-3β, that in turn drives excessive alcohol-drinking behaviors.

Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse

Relapse to alcohol abuse is a critical clinical issue, frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval, during a memory reconsolidation process that depends on protein synthesis. Here, we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar (CeA) inhibition of mTORC1 during reconsolidation disrupts alcohol-cue associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates play a crucial role in alcohol-related memory reconsolidation, and highlight this pathway as a therapeutic target to prevent relapse.

Negative mood, implicit alcohol-related memory, and alcohol use in young adults: The moderating effect of alcohol expectancy

Objective Alcohol-related implicit (preconscious) cognitive processes are established and unique predictors of alcohol use, but most research in this area has focused on alcohol-related implicit cognition and anxiety. This study extends this work into the area of depressed mood by testing a cognitive model that combines traditional explicit (conscious and considered) beliefs, implicit alcohol-related memory associations (AMAs), and self-reported drinking behavior. Method Using a sample of 106 university students, depressed mood was manipulated using a musical mood induction procedure immediately prior to completion of implicit then explicit alcohol-related cognition measures. A bootstrapped two-group (weak/strong expectancies of negative affect and tension reduction) structural equation model was used to examine how mood changes and alcohol-related memory associations varied across groups. Results Expectancies of negative affect moderated the association of depressed mood and AMAs, but there was no such association for tension reduction expectancy. Conclusion Subtle mood changes may unconsciously trigger alcohol-related memories in vulnerable individuals. Results have implications for addressing subtle fluctuations in depressed mood among young adults at risk of alcohol problems.

Disruption of Long-Term Alcohol-Related Memory Reconsolidation: Role of β-Adrenoceptors and NMDA Receptors

Disrupting reconsolidation of drug-related memories may be effective in reducing the incidence of relapse. In the current study we examine whether alcohol-related memories are prone to disruption by the β-adrenergic receptor antagonist propranolol (10 mg/kg) and the NMDA receptor antagonist MK801 (0.1 mg/kg) following their reactivation. In operant chambers, male Wistar rats were trained to self-administer a 12% alcohol solution. After 3 weeks of abstinence, the animals were placed in the self-administration cages and were re-exposed to the alcohol-associated cues for a 20-min retrieval period, immediately followed by a systemic injection of either propranolol, MK801 or saline. Rats were tested for cue-induced alcohol seeking on the following day. Retrieval session, injection and test were repeated on two further occasions at weekly intervals. Both propranolol and MK801 administration upon reactivation did not reduce alcohol seeking after the first reactivation test. However, a significant reduction of alcohol seeking was observed over three post-training tests in propranolol treated animals, and MK801 treated animals showed a strong tendency toward reduced alcohol seeking (p = 0.06). Our data indicate that reconsolidation of alcohol-related memories can be disrupted after a long post-training interval and that particularly β-adrenergic receptors may represent novel targets for pharmacotherapy of alcoholism, in combination with cue-exposure therapies.

Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories

In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

S64-03 Pharmacological disruption of alcohol-related memories - therapeutic impact of the theory of memory reconsolidation

Long-lasting memories that associate environmental stimuli with the effects of alcohol are known to be a main cause of relapse and are a major challenge in the treatment of alcohol addiction. It is reasonable to hypothesize that disrupting consolidated alcohol-related memories might help to prevent relapses. The reconsolidation theory states that a consolidated memory could again become labile and susceptible to disruption by protein synthesis inhibition or NMDA-antagonism after memory retrieval. This has been shown for cocaine- and morphine-associated memories in several recent studies. The aim of our investigations was to examine in an animal model for cue-induced relapse to alcohol-seeking behavior whether the behavioral impact of previously conditioned alcohol associated cues is significantly reduced by blocking the reconsolidation of learned alcohol associations. We show that reconsolidation of alcohol memories is disrupted by post-retrieval ICV-administration of the protein synthesis inhibitor anisomycin. Similarly, post-retrieval i.p.-administration of the NMDA antagonist MK-801 reduced alcohol seeking behavior during the following test day as compared to vehicle treated rats. Pharmacological disruption of reconsolidation of alcohol-associated memories may thus provide a potential therapeutic strategy for the prevention of relapse in alcohol addiction.

Socially mediated alcohol preferences in adolescent rats following interactions with an intoxicated peer

This study focuses on “passive social influences” (alcohol-related information acquired by an organism that interacts with an intoxicated counterpart) that can potentially affect alcohol preference in adolescent rats. Five experiments were conducted to investigate whether repeated social interactions with an intoxicated peer can generate alcohol-related memories that lead an animal to exhibit heightened alcohol olfactory preference patterns. Juvenile experiences with alcohol were operationalized as follows: interactions with an alcohol-intoxicated peer (Experiment 1), with an alcohol-scented cotton surrogate (Experiment 2) or with an anesthetized alcohol-intoxicated partner (Experiments 3–5). Periadolescents were then evaluated in a two-way location olfactory test where they had the opportunity to investigate a hole scented with alcohol odor or vanilla (an odorant naturally preferred by the strain of rats here utilized). Only juveniles that interacted with an alcohol-intoxicated peer were found to exhibit a significant change in alcohol odor preferences when compared to appropriate controls that interacted with a non-intoxicated peer. Alcohol odor exposure alone or interactions with an anesthetized alcohol-intoxicated peer were not sufficient to establish changes in preference for alcohol sensory cues. Results indicate that social interactions with an intoxicated peer determine heightened preference for alcohol cues in periadolescents. The establishment of this preference seems to require behavioral manifestations of the intoxicated counterpart, instead of just being dependent on an olfactory pre-exposure to alcohol cues.

Nursing Experiences With an Alcohol‐Intoxicated Rat Dam Counteract Appetitive Conditioned Responses Toward Alcohol

Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol. Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13. Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning. The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content.

Nursing Experiences With an Alcohol-Intoxicated Rat Dam Counteract Appetitive Conditioned Responses Toward Alcohol

Background: Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol. Methods: Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13. Results: Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning. Conclusions: The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content.

Clinical Use of Benzodiazepines and Decreased Memory Activation in Anxious Problem Drinkers

Clinical use of benzodiazepines (BZDs) may improve treatment outcome in anxious problem drinkers. Decreased activation of alcohol-related memories by negative affective cues may partly explain the beneficial effects of BZDs. To explore this possibility, the present study assessed semantic priming of alcohol words by negative affective words in anxious problem drinkers who received their standard dose of BZD and in unmedicated controls. Two groups of nine subjects each were matched on levels of anxiety, alcohol use, and alcohol dependence before performing a lexical decision task. Medicated subjects displayed significantly less activation than did unmedicated subjects on trials containing negative affective primes and alcohol-related targets, but displayed equivalent activation on control trials with neutral, categorized words. Degree of activation also correlated with a drug's affinity for the BZD receptor. These preliminary results suggest that BZD-induced amnesia may contribute to the therapeutic effects of these drugs in anxious problem drinkers.