Low cognitive flexibility as a risk for heavy alcohol drinking in non-human primates

Abstract

Chronic alcohol abuse is frequently considered a habitual or inflexible behavior; however, measures of pre-existing cognitive flexibility prior to initiation of alcohol use are usually not available. This study used rhesus monkeys and an attentional set-shifting task to investigate whether pre-existing cognitive flexibility would predict increased risk for heavy alcohol drinking. As previously reported, monkeys were given 30 daily set-shifting sessions prior to alcohol access. These sessions consisted of the same sequence of eight unique visual discriminations (sets) of two objects that varied on two dimensions (shapes and colors). The ratio of errors per trials, session duration, and maximum set reached were primary dependent variables from each session and were used to compose a session performance index (PI) that ranged from a low performance PI of 31 to an optimal performance PI of 247. Here, animals underwent an alcohol induction period followed by 22 weeks of daily (22-h) self-administration sessions with free access to water and alcohol. Based on average daily alcohol intake during 22 weeks of 22-h/day access, the monkeys were categorized as non-heavy (mean = 2.0 ± 0.3 g/kg/day; n = 3) and heavy (mean = 3.3 ± 0.5 g/kg/day; n = 6) drinkers. The two groups diverged in performance on the set-shifting task across the 30 pre-alcohol sessions, and at the end of the pre-alcohol testing, the group average PI was 216 ± 27 and 137 ± 71 for the future non-heavy and heavy drinkers, respectively. The data show that low cognitive flexibility assessed with a set-shifting procedure was predictive of future classification as a heavy alcohol drinker. The data highlight individual differences in both cognitive flexibility and in alcohol self-administration in this population of rhesus monkeys.

Chronic Alcohol Drinking Slows Brain Development in Adolescent and Young Adult Nonhuman Primates

“…The low and binge drinkers were collapsed into a group of non-HDs (NHDs; n = 19), and heavy and very heavy drinkers were grouped as HDs ( n = 26). This parallels previous work in humans (Squeglia et al, 2015) and in nonhuman primates (Cervera-Juanes et al, 2017; Shnitko et al, 2019). The third linear mixed model (LMM 3.1) used the categorical variable (group) to determine how heavy and nonheavy alcohol drinking affects age-related changes in volume of the brain, white matter, and gray matter.…”

“…Rhesus macaques have been widely used as a translational model for investigating the neural substrates of human behavior and, particularly, alcohol use and abuse (Grant and Bennett, 2003; Wright and Taffe, 2014; Chandler et al, 2017; Shnitko et al, 2019; Thomas and Czoty, 2019). The present longitudinal study was focused on the measurement of brain changes that occur during late adolescence and early adulthood in rhesus monkeys (3.5–7.5 years of age) because this stage of development confers maximum risk for heavy drinking in humans and macaques (Helms et al, 2014; Substance Abuse and Mental Health Services Administration, 2017).…”

Alcohol Hangover Slightly Impairs Response Selection but not Response Inhibition

“…Importantly, regular binge-drinking does not only increase the likelihood and frequency of hangover, it also strongly increases the risk of developing alcohol use disorder (AUD) [13,14,15]. While it is still unclear whether or how these two consequences are functionally linked, it has been shown that the acute cognitive effects of a high-dose alcohol intoxication resemble the pattern of cognitive deficits observed in AUD patients—both produce pronounced impairments in cognitive control/executive functioning, while behavioural automaticity is comparatively preserved [16,17,18,19,20].…”

Behavioral Flexibility in Alcohol‐Drinking Monkeys: The Morning After

“…Reversals of the correct stimulus were imposed after reaching criteria for acquisition of the discrimination, providing an opportunity to measure an individual's ability to alter their response strategies (i.e., demonstrate cognitive flexibility). Performance on the task predicted future heavy alcohol consumption in rhesus macaques (Shnitko et al, ) and suggests that a reduced ability to optimize behavior when contingencies change is a predisposing factor to heavy drinking. To extend these results, the present study is focused on the consequences of chronic alcohol drinking on behavioral flexibility in this same cohort of rhesus monkeys.…”

“…Cognitive and sensory‐motor domains of behavioral flexibility were assessed with the SST. In this longitudinal design, first retention of the SST was measured (Shnitko et al, ), and then, a sensory‐motor challenge to the SST was assessed by decreasing the size of the visual stimuli. A similar approach has been used in human subjects where recognition of visual shapes was influenced by the size of the shapes presented (Jolicoeur, ).…”