The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour.

The effects of ethanol on the brain are concentration dependent. Low concentrations (mM) intoxicate, while greater than 100 mM anaesthetize. Of most relevance to human alcohol addiction are mechanisms of intoxication. Previously, Caenorhabditis elegans has been employed in genetic screens to define effectors of intoxication. Here, we inform interpretation of these studies by providing evidence that ethanol rapidly equilibriates across C. elegans cuticle. Importantly, the effect of ethanol on muscle activity rapidly reaches steady-state, and the concentration-dependence of the effect is very similar in intact animals and exposed muscle. Thus the cuticle does not present an absorption barrier for ethanol, and furthermore the internal concentration is likely to approach that applied externally. Thus, modelling intoxication in C. elegans requires exposure to external ethanol less than 100 mM. Furthermore, the permeability of the cuticle to ethanol enables analysis of precisely controlled concentration-dependent effects of acute, chronic, and episodic ethanol exposure on behaviour.

Facial electromyographic (EMG) responses to emotionally significant visual images: differences between light and heavy drinkers.

Fifty participants took part in an experiment designed to investigate individual differences in the effects of alcohol on facial EMG responses to emotionally significant stimuli. Participants took part in two experimental sessions during which they viewed emotionally negative and emotionally positive visual images. In one session they consumed alcohol (0.5 g/kg bodyweight) whilst in the other they consumed soft drink. We classified each participant as a light or heavy drinker on the basis of their self-reported alcohol consumption. Negatively valenced images elicited increases in both frontalis and corrugator activity but alcohol did not moderate this effect either in light or heavy drinkers. Nevertheless, heavy drinkers did respond more strongly to the negatively valenced images and this supports the view that responses to negative emotional stimuli may play a part in the development of heavy drinking as a result of negative reinforcement processes.

Motivation for alcohol assessed by multiple variable interval schedule behaviour: effects of reward size and alcohol cues.

Altered motivation for drugs of abuse is a central feature of most definitions of drug dependence and the impact of drug-related cues on motivation is of current interest. However, since most studies of cue-reactivity have not used behavioural measures of motivation, their results are often difficult to interpret in motivational terms. In the current paper we describe two experiments in which a behavioural technique, based on multiple variable interval (VI) schedules of reinforcement, was used to study motivation for alcohol in human subjects. In both experiments, subjects attended for several sessions and, during each session, were exposed to a 6-ply VI schedule (values ranged from 1 to 720 s), during which they earned points that were later exchanged for a preferred beer or lager. In Experiment 1 the procedure was validated by showing that changes in the magnitude of reinforcement altered behaviour appropriately. In Experiment 2 we found evidence that the presence of an alcohol-related cue increased the value of alcohol rewards. The results are discussed with reference to a model for the behavioural effects of drug-related cues in triggering relapse and a number of problems we found in using the multiple variable interval schedule procedure.

Flavour conditioning and alcohol: a multilevel model of individual differences.

Previous research shows that dependent drinkers respond more strongly to alcohol-related cues and suggests that alcohol cue-reactivity may be relevant to understanding dependence liability. However, a significant weakness in many studies is the fact that cue-reactivity is studied without actually conditioning subjects; responses to alcohol-related cues are simply assumed to be conditioned responses. The current report attempts to overcome this weakness by studying alcohol cue-reactivity following a flavour-conditioning procedure. A statistical model of individual differences in cue-reactivity was constructed using previous alcohol exposure, alcohol tolerance, and personality as predictor variables. Although there was no evidence for overall differences in subjective and psychophysiological responses to alcohol and soft-drink paired flavours, there were marked individual differences in responding to the different flavours. The statistical model showed that reward sensitivity (high extroversion, high neuroticism), heavier levels of drinking, and higher levels of tolerance to the intoxicating effects of alcohol were associated with lower levels of skin conductance in the presence of alcohol paired flavours.

Activation of alcohol-related associative networks by recent alcohol consumption and alcohol-related cues.

AIMS: To investigate the influence of recent alcohol consumption and alcohol-related cues on performance in a sentence generation task. DESIGN: Two experiments were carried out. In the first, the performances of light, moderate and heavy drinkers were compared. In the second, subjects were randomly assigned to one of three experimental treatments (alcohol-priming, non-alcohol priming, and control) and classified as light, moderate or heavy drinkers. The effect of experimental treatment, drinking status, gender and the interaction between these factors was studied. SETTING: The experiments were carried out in quiet research rooms in psychology departments. PARTICIPANTS: Volunteers recruited from university campuses. MEASUREMENTS: Questionnaires were used to ascertain recent drinking histories. Subjects generated sentences incorporating ambiguous alcohol-related words which were provided by the experimenter. The sentences were then classified as alcohol-related or not, the dependent measure was the number of alcohol-related sentences produced. FINDINGS: In both experiments heavier drinkers produced more alcohol-related sentences and males produced more alcohol-related sentences than females. In the second experiment more alcohol-related sentences were produced after subjects were exposed the alcohol priming condition. CONCLUSIONS: The alcohol-related meaning of ambiguous words is more likely to be accessed by males and by heavier drinkers and after exposure to other alcohol cues.

Multiple variable interval schedule behaviour in humans: effects of ethanol, mood, and reinforcer size on responding maintained by monetary reinforcement.

Ethanol is an effective reinforcer but, in common with other drugs of abuse, it may derive some of its reinforcing properties from the effects it has on behaviour maintained by other reinforcers. However, any assessment of ethanol's hypothesized effect on behaviour maintained by other reinforcers must take into account the fact that ethanol may have multiple mechanisms of action. In order to address this problem the experiments reported herein used a procedure based upon Herrnstein's Matching Law which allowed joint assessment of subjects' motor capacity and reinforcer sensitivity. The effect of ethanol (0, 0.3, and 0.6 g/kg) on motor capacity and reinforcer sensitivity was assessed by studying behaviour maintained by monetary reinforcement. In the first experiment the procedure was validated by showing that the behaviour of subjects was sensitive to changes in reinforcer value and in the second experiment 0.6 g/kg ethanol reduced motor capacity but did not affect reinforcer sensitivity. As a secondary hypothesis we also studied the effect of mood on reinforcer sensitivity and motor capacity. It was found that lower mood scores (lower hedonic tone) were associated with reduced reinforcer sensitivity and that male subjects showed higher motor capacity than females. However, there was also a mood by sex interaction, which indicated that higher motor capacity in males was only found in the presence of lower mood scores. The results are discussed in relation to the mechanisms of ethanol's dopaminergic effects, interactions between ethanol and other drugs of abuse, and the changes in reinforcer sensitivity which are thought to occur in depression.

The effect of drink familiarity on tolerance to alcohol.

Cues associated with familiar alcoholic drinks such as beer may, through repeated association with the unconditioned stimulus properties of alcohol, acquire the status of classically conditioned stimuli. It has been proposed that such drug-related conditioned stimuli mediate drug tolerance. Thus, the aim of the present experiment was to test this proposition on cognitive, subjective, and psychophysiological indicators of alcohol tolerance using human subjects. Two groups of subjects received alcohol in the form of a familiar drink (beer) or an unfamiliar drink (blue peppermint mixture). Both drinks contained the same dose of alcohol and were consumed at the same rate. Although conditioned heart rate and skin conductance responses occurring while subjects looked at and tasted the test drinks were weak, there were strong indicators of conditioned tolerance on the performance measures following consumption. Subjects who consumed the unfamiliar drink were significantly poorer on cognitive and motor tasks, and they rated themselves more intoxicated than did those who consumed the familiar drink.

The biological, social and clinical bases of drug addiction: commentary and debate.

This article summarizes the main discussions at a meeting on the biological, social and clinical bases of drug addiction focused on contemporary topics in drug dependence. Four main domains are surveyed, reflecting the structure of the meeting: psychological and pharmacological factors; neurobiological substrates; risk factors (including a consideration of vulnerability from an environmental and genetic perspective); and clinical treatment. Among the topics discussed were tolerance, sensitization, withdrawal, craving and relapse; mechanisms of reinforcing actions of drugs at the behavioural, cognitive and neural levels; the role of subjective factors in drug dependence; approaches to the behavioural and molecular genetics of drug dependence; the use of functional neuroimaging; pharmaceutical and psychosocial strategies for treatment; epidemiological and sociological aspects of drug dependence. The survey takes into account the considerable disagreements and controversies arising from the discussions, but also reaches a degree of consensus in certain areas.

Alcohol and the reward value of cigarette smoking.

People who drink alcohol are more likely to smoke, and experiments have shown that alcohol can increase cigarette smoking. However, it is not clear why alcohol consumption should increase smoking. To address this issue the current experiment looked at the effects of alcohol on a range of behavioural and subjective measures intended to assess the reward value of smoking. These included a preference test carried out after subjects had smoked cigarettes of one colour after consuming alcohol, and cigarettes of another colour after consuming non-alcoholic drinks. In the preference test, subjects were offered the choice of smoking the alcoholic or non-alcoholic drink-paired cigarette. It was hypothesised that if alcohol increased the reward value of smoking, subjects would choose to smoke the alcohol-paired cigarette. Consumption of alcohol increased the length of time people spent smoking, increased the number of puffs taken on each cigarette, and increased the amount of tobacco burnt. There were also strong subjective effects, with subjects looking forward more to smoking after alcohol and reporting greater smoking satisfaction after alcohol. However, subjects did not show a preference for the cigarettes they had smoked after alcohol.

Alcohol as an unconditioned stimulus in human classical conditioning.

Recent experiments with human subjects have shown that drug cues (e.g. sight of beer or needle and syringe) elicit different responses than do neutral stimuli. However, because conditioning has not been carried out in the majority of cases, it is not clear why drug cues have different response eliciting capacities; associative and nonassociative mechanisms may both play a part. In this experiment a counterbalanced differential conditioning procedure was used to isolate the role of associative processes in the development of physiological, behavioural, and subjective conditioned responses to cues for alcohol over the course of repeated conditioning sessions. Twelve healthy volunteers took part in the experiment which involved each subject attending for ten sessions. On physiological measures evidence was found for conditioning of skin conductance and cardiac inter-beat interval responses to cues for alcohol delivery. Over the course of conditioning on behavioural measures of drink consumption there were changes in the rate of consumption and number of sips taken as a function of whether or not the drinks contained alcohol. Finally, on subjective measures, there was a differential change in subjective state in response to alcohol and soft drink expectancy as conditioning progressed.

A controlled trial of cue exposure treatment in alcohol dependence.

The clinical effectiveness of cue exposure (CE) treatment in alcohol dependence was evaluated in a controlled trial. Thirty-five men who were detoxified and severely alcohol dependent received either CE or relaxation control (RC) treatment. CE Ss had 400 min exposure to the sight and smell of preferred drinks over 10 days in a laboratory setting. RC Ss spent identical time in the laboratory but had relaxation therapy and only 20 min exposure to alcohol cues. During 6-month follow-up, personal interview was achieved with 91% of Ss. CE Ss had a more favorable outcome than the RC Ss in terms of latency (length of time) to relapse of heavy drinking (p < .01) and total alcohol consumption (p < .05). Significant predictors of latency to heavy drinking and dependence included skin conductance level (p < .001) and experimental condition (p < .01). Results point to the potential importance of cue exposure as a treatment for addictive behavior.

Alcohol dependence and cue reactivity.

A group of 35 severely dependent male alcoholic patients undergoing cue exposure treatment were studied. Thirty-one subjects had complete data and their physiological and subjective responses to drink cues on the first day of the cue exposure program were subjected to a principal components analysis. The principal component loadings were then used to construct a single measure of responsivity and this responsivity measure was found to correlate significantly with Severity of Alcohol Dependence Questionnaire (SADQ) scores. Further analysis of the relationship between responsivity and the subscales of the SADQ showed that the experience of affective withdrawal symptoms, craving for alcohol and drinking to relieve withdrawal symptoms were the most strongly correlated with responsivity.

A conditioning approach to the analysis and treatment of drinking problems.

Drinking problems are a major public health concern and a significant part of this concern arises because drinking habits are very difficult to change once established; although many patients can detoxify successfully there is a high rate of relapse. This chapter describes the analysis and treatment of drinking problems using a behavioural approach based on the concepts and methods of classical conditioning. Recent evidence shows that alcoholic patients show a variety of physiological and subjective responses to the presentation of alcoholic drink cues and these responses may play a part in the regulation of drinking behaviour. The implication is that cue-exposure treatments ought to reduce drinking. In cue-exposure, responses to drink cues are extinguished by repeated presentation of the cue without allowing subsequent consumption of alcohol. The empirical evidence for the effectiveness of such treatments is described and the current status of the approach to the analysis and treatment of drinking problems will be summarised.

A method for producing alcohol placebos.

A method for producing placebo drinks that are hard to discriminate from alcoholic drinks is described. Subjects received a series of paired comparisons, each involving a distinctively flavoured alcoholic drink and one of six different placebo versions of it. Following each such comparison, rating scales were used to record the 'alcoholic strength' and 'sensory intensity' of a placebo drink relative to the alcoholic drink. The procedure was replicated using another distinctive alcoholic drink and another set of placebos. Based upon a multivariate analysis of subjects' ratings, the version of the placebo that was most difficult to discriminate from it's corresponding alcoholic drink was identified for both alcoholic drinks. The method is intended to be a general one for producing placebo versions of alcoholic drinks which do not differ on any dimensions which can be shown to be important in producing a response.

Different drink cues elicit different physiological responses in non-dependent drinkers.

Different kinds of physiological response to stimuli which have been associated with alcohol ingestion have been observed in human subjects. A literature review shows that when subjects are exposed to alcohol associated stimuli without consuming the drinks then increases in arousal, as indexed by skin conductance and heart rate increases, tend to occur. If subjects consume drinks which have been associated with alcohol ingestion, then decreases in arousal tend to occur. Forty non-dependent drinkers were asked to either consume or hold drinks which either had a history of alcohol association or did not. Interactions were observed between the activities subjects engaged in with the drinks and the degree of alcohol association of the drinks. Presentation of alcohol associated drinks produced smaller increases in arousal than non-alcohol associated drinks if the drinks were consumed but vice versa if the drinks were just held. The results support the conclusions drawn from the literature review and have implications for current theories of conditioned responses to drug cues and the related theories of the motivational processes involved in the regulation of drug intake.

Conditioned learning in alcohol dependence: implications for cue exposure treatment.

A review of the literature pertinent to cue exposure treatment in alcohol dependence is presented. Psychological models of relapse, based on conditioning and social learning theories, are critically evaluated. In particular, attention is drawn to the potential implications for cue exposure research and treatment of an interaction between Pavlovian and operant conditioning, problems with the application of the concepts of arousal and craving and the importance of a systems model to understand physiological responses. It is concluded that no study has so far demonstrated a link between conditioned responses to alcohol-related cues and relapse, an assumption on which cue exposure treatment is based. Further, the evidence for the effectiveness of cue exposure as a treatment is lacking. Promising research directions are identified.