Abigail K. Rose

Different types of nutritional deficiencies affect different domains of spatial memory function checked in a radial arm maze

Several studies using animal models have suggested that the effects of nutritional insult on the developing brain are long-lasting and lead to permanent deficits in learning and behavior. Malnutrition can refer to the availability of all the nutrients but in insufficient quantities or it may imply that one or more of essential nutrients is either missing or is present, but in the wrong proportions in the diet. The hypothesis addressed in this study is that different domains of cognitive functioning can be affected by malnutrition and this can be related to the type of nutritional deficiency that the brain has been exposed to during development. To study the effect of nutritional deprivation during brain development, a paradigm of maternal malnutrition during the period of gestation and lactation was used and its effects were studied on the F1 offspring using Swiss albino mice. Three different types of malnutrition were used, that involve, caloric restriction, inadequate amount of protein in the diet and condition of low iron content. Our results show that the domain of spatial memory affected in the F1 generation depended on the kind of malnutrition that the mother was subjected to. Further our study shows that although hippocampal volume was reduced in all F1 pups, hippocampal subregions of the F1 animals were differentially vulnerable depending on type of malnutrition that the mother was subjected to. These results highlight the importance of qualifying the kind of malnutrition that is suffered by the mother during the period of gestation and lactation as it has consequences for the cognitive domain affected in the offspring. Awareness of this should inform prevention strategies in trying to reverse the effects of adverse maternal nutrition during critical periods in brain development.

Effects of alcohol on inhibitory processes.

Earlier work has shown that alcohol may have disinhibiting effects on behaviour. Two studies tested the effects of a moderate dose of alcohol (0.6 g/kg) versus placebo on tasks that evaluate inhibitory processes related to alcohol stimuli, in moderate-to-heavy social drinkers (student population). An inhibition of interference task, the Stroop task (ST; study 1), and an inhibition of a prepotent response task, the go/no-go task (GNG; study 2), were used. The effects of alcohol on working memory function were also examined. Participants preloaded with alcohol made more errors on the colour and alcohol ST than those preloaded with placebo. In the GNG task, responding to alcohol-related pictures was slower than responding to neutral pictures. When participants were required to switch responding from neutral to alcohol-related go stimuli, responding became slower; however, responding to alcohol go stimuli became faster as time progressed; no effect of alcohol was found. Alcohol had no effect, compared with placebo, on the working memory tasks. Therefore, a moderate dose of alcohol had restricted effects on inhibitory processes: only interference inhibition measured in the ST was affected. Although the data obtained with the GNG task did not show an effect of alcohol on response inhibition, increased latency of response in the presence of alcohol-related stimuli compared with neutral stimuli indicates that alcohol stimuli are more salient to social drinkers, attracting a greater amount of attention.

The Subjective, Rather Than the Disinhibiting, Effects of Alcohol Are Related to Binge Drinking

BACKGROUND Evidence suggests that alcohol-related problems are associated with impulsivity and disinhibited behavior. Less certain is whether disinhibited behavior is due to an impulsive disposition or alcohols ability to disinhibit some people more than others. There are a range of disinhibited behaviors associated with alcohol, including excessive alcohol consumption, bingeing. The study tested whether nondependent alcohol bingers showed more disinhibition after placebo and/or alcohol relative to nonbingers and whether this was related to enhanced motivation to drink following a priming dose of alcohol. METHODS Twenty participants (10 bingers) attended the laboratory twice. Baseline measures included impulsivity, alcohol-related cognitions, alcohol urge, and mood. Participants were preloaded with alcohol (male: 0.6 g/kg, female: 0.5 g/kg) and placebo (counterbalanced). After a 20-minute rest, participants completed 2 impulsivity tasks (Two Choice & Time Estimation) separated by second urge and mood ratings. RESULTS Bingers did not show greater impulsivity characteristics but were more concerned about their drinking (p = 0.02) and ability to control drinking (p = 0.04). A priming effect was found: alcohol urge increased after alcohol but not placebo (p = 0.006). Bingers reported greater tolerance to the sedative (p = 0.05) and lightheaded (p = 0.04) effects of alcohol, relative to nonbingers. Binge status was not associated with impulsivity task performance, while preload type (alcohol/placebo) supported only marginal associations. CONCLUSIONS Risk of binge drinking in nondependent individuals is not strongly affected by impulsive personality characteristics or alcohols ability to induce behavioral disinhibition. However, alcohol did lead to a priming effect and bingers were more tolerant to the sedative and lightheaded effects of alcohol relative to placebo. Risk of binge drinking is associated with the subjective effects of a priming dose of alcohol.

Electrophysiological responses to alcohol cues are not associated with Pavlovian-to-instrumental transfer in social drinkers.

Pavlovian to Instrumental Transfer (PIT) refers to the behavioral phenomenon of increased instrumental responding for a reinforcer when in the presence of Pavlovian conditioned stimuli that were separately paired with that reinforcer. PIT effects may play an important role in substance use disorders, but little is known about the brain mechanisms that underlie these effects in alcohol consumers. We report behavioral and electroencephalographic (EEG) data from a group of social drinkers (n = 31) who performed a PIT task in which they chose between two instrumental responses in pursuit of beer and chocolate reinforcers while their EEG reactivity to beer, chocolate and neutral pictorial cues was recorded. We examined two markers of the motivational salience of the pictures: the P300 and slow wave event-related potentials (ERPs). Results demonstrated a behavioral PIT effect: responding for beer was increased when a beer picture was presented. Analyses of ERP amplitudes demonstrated significantly larger slow potentials evoked by beer cues at various electrode clusters. Contrary to hypotheses, there were no significant correlations between behavioral PIT effects, electrophysiological reactivity to the cues, and individual differences in drinking behaviour. Our findings are the first to demonstrate a PIT effect for beer, accompanied by increased slow potentials in response to beer cues, in social drinkers. The lack of relationship between behavioral and EEG measures, and between these measures and individual differences in drinking behaviour may be attributed to methodological features of the PIT task and to characteristics of our sample.

The Importance of Glucocorticoids in Alcohol Dependence and Neurotoxicity

Alterations in hypothalamo-pituitary adrenal (HPA) function have been described in alcoholics and in rodents after chronic alcohol consumption but the role of glucocorticoids in alcohol consumption, and the mechanisms involved, has received little attention until recently. Both alcohol consumption and withdrawal from chronic alcohol intake raise circulating glucocorticoid levels, and prolonged high concentrations of glucocorticoids are known to have detrimental effects on neuronal function and cognition. This minireview covers the ways in which glucocorticoids may be involved in drinking behavior, from social drinking to dependence, and the negative consequences of alcohol consumption seen during withdrawal which may have a detrimental effect on treatment outcome. Research shows prolonged increases in brain glucocorticoid concentrations and decreased brain glucocorticoid receptor availability (consistent with increased levels of endogenous ligand) after withdrawal from chronic alcohol treatment. Evidence suggests that increased glucocorticoid levels in the brain after chronic alcohol treatment are associated with the cognitive deficits seen during abstinence which impact on treatment efficacy and quality of life. Studies on organotypic cultures also demonstrate the importance of glucocorticoids in the neuropathological consequences of alcohol dependence.

Extinction of cue-evoked drug-seeking relies on degrading hierarchical instrumental expectancies

There has long been need for a behavioural intervention that attenuates cue-evoked drug-seeking, but the optimal method remains obscure. To address this, we report three approaches to extinguish cue-evoked drug-seeking measured in a Pavlovian to instrumental transfer design, in non-treatment seeking adult smokers and alcohol drinkers. The results showed that the ability of a drug stimulus to transfer control over a separately trained drug-seeking response was not affected by the stimulus undergoing Pavlovian extinction training in experiment 1, but was abolished by the stimulus undergoing discriminative extinction training in experiment 2, and was abolished by explicit verbal instructions stating that the stimulus did not signal a more effective response-drug contingency in experiment 3. These data suggest that cue-evoked drug-seeking is mediated by a propositional hierarchical instrumental expectancy that the drug-seeking response is more likely to be rewarded in that stimulus. Methods which degraded this hierarchical expectancy were effective in the laboratory, and so may have therapeutic potential.

A comparison of the anticipated and pharmacological effects of alcohol on cognitive bias, executive function, craving and ad-lib drinking

Acute alcohol administration alters automatic processing of alcohol-related cues, impairs executive functions and increases alcohol seeking. Few studies have investigated the effects of expecting to receive alcohol on these measures. Thirty-one social drinkers completed three experimental sessions receiving either 0.65 g/kg alcohol, a placebo and a control beverage (which they knew was not alcoholic) before reporting craving and completing a test battery including a measure of automatic alcohol-approach tendencies (stimulus response compatibility task), a measure of executive function (Controlled Oral Word Association Task (COWAT)) and a taste test assessing ad-lib drinking. Results indicated that alcohol administration impaired performance on the COWAT and increased ad-lib drinking; however, there were no significant differences on these measures after administration of placebo versus control beverages. Craving was increased after alcohol and (to a lesser extent) after placebo. Automatic alcohol-approach tendencies were pronounced after both alcohol and placebo compared to the control beverage, with no difference between alcohol and placebo. Results suggest craving is sensitive to the anticipated and pharmacological effects of alcohol, alcohol-approach tendencies are particularly sensitive to the anticipated effects of alcohol, and measures of executive function and ad-lib drinking are affected by the pharmacological, but not the anticipated, effects of alcohol.

Phasic transition from goal-directed to habitual control over drug-seeking produced by conflicting reinforcer expectancy.

The transition from goal‐directed to habitual control over drug‐seeking has been experimentally demonstrated in animals, but there have been no comparable reports in humans. Following a recent animal design, the current study employed an outcome‐devaluation procedure to test whether goal‐directed control over tobacco seeking would be abolished by alcohol expectancy. Eighty smokers first learned that two responses earned tobacco or chocolate points, respectively, before tobacco was devalued by health warnings and smoking satiety. Participants were then presented with either a glass of beer/wine or water with instructions that this item could be consumed after the task (alternative reward). Then choice between the tobacco and chocolate response was measured in extinction to assess goal‐directed control of tobacco seeking, in a nominal Pavlovian to instrumental transfer (PIT) test to assess stimulus control of tobacco seeking, and in a reacquisition test to assess the impact of direct feedback from the outcomes. The results showed that alcohol expectancy selectively abolished goal‐directed control of tobacco seeking but not stimulus control or the impact of feedback from outcomes. These data suggest that ‘endogenous’ retrieval of low drug value governing goal‐directed regulation of drug seeking is disrupted by conflicting appraisal of an alternative reinforcer, promoting habitual control, which may play a role in relapse.

Reward expectancy promotes generalized increases in attentional bias for rewarding stimuli.

Expectations of drug availability increase the magnitude of attentional biases for drug-related cues. However, it is unknown whether these effects are outcome specific, or whether expectation of a specific reinforcer produces a general enhancement of attentional bias for other types of rewarding cues. In the present study, 31 social drinkers completed an eye-tracking task in which attentional bias for alcohol- and chocolate-related cues was assessed while the expectation of receiving alcohol and chocolate was manipulated on a trial-by-trial basis. Participants showed attentional bias for alcohol and chocolate cues (relative to neutral cues) overall. Importantly, these attentional biases for reward cues were magnified when participants expected to receive alcohol and chocolate, but effects were not outcome specific: The expectation of receiving either alcohol or chocolate increased attentional bias for both alcohol and chocolate cues. Results suggest that anticipation of reward produces a general rather than an outcome-specific enhancement of attentional bias for reward-related stimuli.

The ad-libitum alcohol ‘taste test’: secondary analyses of potential confounds and construct validity

RationaleMotivation to drink alcohol can be measured in the laboratory using an ad-libitum ‘taste test’, in which participants rate the taste of alcoholic drinks whilst their intake is covertly monitored. Little is known about the construct validity of this paradigm.ObjectiveThe objective of this study was to investigate variables that may compromise the validity of this paradigm and its construct validity.MethodsWe re-analysed data from 12 studies from our laboratory that incorporated an ad-libitum taste test. We considered time of day and participants’ awareness of the purpose of the taste test as potential confounding variables. We examined whether gender, typical alcohol consumption, subjective craving, scores on the Alcohol Use Disorders Identification Test and perceived pleasantness of the drinks predicted ad-libitum consumption (construct validity).ResultsWe included 762 participants (462 female). Participant awareness and time of day were not related to ad-libitum alcohol consumption. Males drank significantly more alcohol than females (p < 0.001), and individual differences in typical alcohol consumption (p = 0.04), craving (p < 0.001) and perceived pleasantness of the drinks (p = 0.04) were all significant predictors of ad-libitum consumption.ConclusionsWe found little evidence that time of day or participant awareness influenced alcohol consumption. The construct validity of the taste test was supported by relationships between ad-libitum consumption and typical alcohol consumption, craving and pleasantness ratings of the drinks. The ad-libitum taste test is a valid method for the assessment of alcohol intake in the laboratory.