Persistent negative effects of alcohol drinking on aspects of novelty-directed behavior in male rhesus macaques

Abstract

Humans with histories of prolonged heavy alcohol use exhibit poorer performance on cognitive tasks associated with problem solving, short-term memory, and visuospatial reasoning, even following the cessation of drinking, when compared with healthy controls. It is unclear, however, whether the cognitive problems are a consequence of alcohol exposure or a contributing factor to alcohol-use disorders. Here, we examined the relationship between performance on a novel object recognition (NOR) task and total alcohol consumption (TAC) in adult male rhesus macaques (n = 12; ETH group; trained to self-administer alcohol). NOR performance in this group was assessed prior to induction of alcohol drinking (“pre”) and, again, after a 1-year abstinence period (“post”) and was compared to the performance of a second group (n = 6; Control group), which was alcohol-naïve. In the NOR task, difficulty was manipulated across three phases by varying specific object features and/or by varying duration of access to objects. For each monkey, we measured aspects of novelty-related behavior including novelty detection, novelty reactivity, and perseverative behavior. TAC during induction and a “free” access period in which the monkey could choose between water and a 4% w/v ethanol solution also was determined. We found that performance deficits in the NOR task were a consequence of high total alcohol intake instead of a predictor of subsequent high intake. Poor NOR performance in drinkers with the highest intakes was characterized by increased perseverative behavior rather than an inability to detect or react to novelty. Finally, the observed deficits are long-lasting – persisting even after a year of abstinence. Given the prevalent and persistent nature of alcohol-induced cognitive deficits in patients in treatment settings, understanding the nature of the deficit and its neural basis could ultimately offer novel treatment approaches based on the reversal of alcohol-induced impairment.

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

“…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).…”

Behavioral Flexibility in Alcohol‐Drinking Monkeys: The Morning After

“…The majority of previous studies that explored alcohol effects on cognitive flexibility were done with rodents, using a cross‐sectional study design, and demonstrated that EtOH exposure (vapor cambers, intragastric injections) attenuates cognitive flexibility (e.g., Gass et al, ; Sey et al, ). Additionally, in nonhuman primate models of alcohol drinking, chronic alcohol attenuated major executive functions supporting behavioral flexibility, such as working memory, visual discrimination, response time, and accuracy (Chandler et al, ; Crean et al, ; Taffe et al, ; Wright and Taffe, ). In this study, following the chronic alcohol consumption, monkeys, as a group, had nearly identical performance as a control group on the set‐shift task assessed in a sober condition when the testing parameters were the same as before alcohol drinking (Fig.…”

The Effect of Chronic Alcohol on Cognitive Decline: Do Variations in Methodology Impact Study Outcome? An Overview of Research From the Past 5 Years

“…Performance in the novel object recognition task was also associated with alcohol consumption in adult male rhesus macaques (4–6 years old) ( Chandler et al, 2017 ). Monkeys were trained in an operant self-administration protocol the same as above, then allowed an additional month of free access to water and alcohol for 3 h per day.…”