Dataset Information

Behavioral Flexibility in Alcohol-Drinking Monkeys: The Morning After.

ABSTRACT: BACKGROUND:Heavy alcohol drinking has aspects of inflexible behavior. This study addressed the consequences of chronic alcohol drinking on cognitive and sensory-motor domains of behavioral flexibility in rhesus monkeys. METHODS:Behavioral flexibility was assessed in 12 monkeys (n = 9, ethanol [EtOH] drinkers) with a set-shifting visual discrimination procedure before alcohol self-administration and while maintaining consumption of 1.5 g/kg/d EtOH. Task performance was assessed in the morning after ~18 hours of drinking 1.5 g/kg, and 1 hour before the next day's drinking session began. The first 10 set-shifting sessions had the original (preethanol) test parameters and were used to determine retention of preethanol performance. Then, an effect of sensory-motor challenge (60% reduction in the size of the discriminative stimuli) on performance was assessed during 10 additional sessions. RESULTS:There were no average group-dependent differences in the performance between control and EtOH groups at the preethanol time-point. The daily consumption of 1.5 g/kg/d produced binge alcohol intakes in 7 of 9 monkeys (blood EtOH concentration [BEC ? 80 mg/dl]). Chronic daily intakes of 1.5 g/kg had no effect on retention of the task in the sober state. However, when challenged with a reduction in the size of the stimuli, daily 1.5 g/kg EtOH resulted in a decrement in performance due to an increase in the number of errors. CONCLUSIONS:Rhesus monkeys consuming 1.5 g/kg alcohol daily perform equally as could as control monkeys in retention of a well-learned cognitive task. However, this pattern of daily alcohol intake robustly decreased the ability to flexibly adjust behavior when confronted with novel changes to perceptual stimuli.

SUBMITTER: Shnitko TA

PROVIDER: S-EPMC7236888 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Behavioral Flexibility in Alcohol-Drinking Monkeys: The Morning After.

Shnitko Tatiana A TA Gonzales Steven W SW Newman Natali N Grant Kathleen A KA

Alcoholism, clinical and experimental research 20200218 3

<h4>Background</h4>Heavy alcohol drinking has aspects of inflexible behavior. This study addressed the consequences of chronic alcohol drinking on cognitive and sensory-motor domains of behavioral flexibility in rhesus monkeys.<h4>Methods</h4>Behavioral flexibility was assessed in 12 monkeys (n = 9, ethanol [EtOH] drinkers) with a set-shifting visual discrimination procedure before alcohol self-administration and while maintaining consumption of 1.5 g/kg/d EtOH. Task performance was assessed in ...[more]

PMID: 31984521

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Project description:BackgroundThe Monkey Alcohol Tissue Research Resource (MATRR) is a repository and analytics platform for detailed data derived from well-documented nonhuman primate (NHP) alcohol self-administration studies. This macaque model has demonstrated categorical drinking norms reflective of human drinking populations, resulting in consumption pattern classifications of very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD) individuals. Here, we expand on previous findings that suggest ethanol drinking patterns during initial drinking to intoxication can reliably predict future drinking category assignment.MethodsThe classification strategy uses a machine-learning approach to examine an extensive set of daily drinking attributes during 90 sessions of induction across 7 cohorts of 5 to 8 monkeys for a total of 50 animals. A Random Forest classifier is employed to accurately predict categorical drinking after 12 months of self-administration.ResultsPredictive outcome accuracy is approximately 78% when classes are aggregated into 2 groups, "LD and BD" and "HD and VHD." A subsequent 2-step classification model distinguishes individual LD and BD categories with 90% accuracy and between HD and VHD categories with 95% accuracy. Average 4-category classification accuracy is 74%, and provides putative distinguishing behavioral characteristics between groupings.ConclusionsWe demonstrate that data derived from the induction phase of this ethanol self-administration protocol have significant predictive power for future ethanol consumption patterns. Importantly, numerous predictive factors are longitudinal, measuring the change of drinking patterns through 3 stages of induction. Factors during induction that predict future heavy drinkers include being younger at the time of first intoxication and developing a shorter latency to first ethanol drink. Overall, this analysis identifies predictive characteristics in future very heavy drinkers that optimize intoxication, such as having increasingly fewer bouts with more drinks. This analysis also identifies characteristic avoidance of intoxicating topographies in future low drinkers, such as increasing number of bouts and waiting longer before the first ethanol drink.

Project description:BackgroundAlcohol's ability to potentiate the activity of γ-aminobutyric acid (GABA) at GABAA receptors has been implicated as a key mechanism underlying the behavioral effects of alcohol. The complex molecular biology of these receptors raises the possibility that particular receptor subtypes may play unique roles in alcohol's abuse-related effects and that subtype-selective ligands with therapeutic specificity against alcohol might be developed. This study evaluated the capacity of α5GABAA receptor ligands to alter selectively the reinforcing effects of alcohol.MethodsTwo groups of rhesus monkeys were trained to orally self-administer alcohol or sucrose under fixed-ratio schedules and limited daily access conditions. In addition, following daily self-administration sessions, the behavior of each monkey was scored for both species-typical and drug-induced behaviors.ResultsConcentrations of 1 to 6% alcohol maintained self-administration above water levels, engendered pharmacologically relevant blood alcohol levels ranging from 90 to 160 mg/dl, and produced changes in behavior typical of alcohol intoxication. Concentrations of 0.3 to 3% sucrose also reliably maintained self-administration. The α5GABAA receptor agonist QH-ii-066 enhanced and the α5GABAA receptor inverse agonist L-655,708 inhibited alcohol, but not sucrose drinking. The changes in alcohol drinking could be reversed with the α5GABAA receptor antagonist XLi-093. However, L-655,708 increased yawning in both alcohol and sucrose drinkers, possibly indicative of an anxiogenic effect.ConclusionsThese findings suggest a prominent and specific role for α5GABAA receptor mechanisms in the reinforcing effects of alcohol. Moreover, these results suggest that α5GABAA receptors may represent a novel pharmacological target for the development of medications to reduce drinking. Of ligands modulating this receptor, α5GABAA receptor inverse agonists may hold the most promise as alcohol pharmacotherapies.

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Behavioral Flexibility in Alcohol-Drinking Monkeys: The Morning After.

Publications

Behavioral Flexibility in Alcohol-Drinking Monkeys: The Morning After.

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