Impaired Response Inhibition in the Rat 5 Choice Continuous Performance Task during Protracted Abstinence from Chronic Alcohol Consumption

Abstract

Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT) and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavioral inhibition during alcohol abstinence are sparse. The present study employed the rat 5 Choice-Continuous Performance Task (5C-CPT), a novel pre-clinical variant of the CPT, to evaluate attentional capacity and impulse control over the course of protracted abstinence from chronic intermittent alcohol consumption. In tests conducted with familiar 5C-CPT conditions EtOH-exposed rats exhibited impaired attentional capacity during the first hours of abstinence and impaired behavioral restraint (increased false alarms) during the first 5d of abstinence that dissipated thereafter. Subsequent tests employing visual distractors that increase the cognitive load of the task revealed significant increases in impulsive action (premature responses) at 3 and 5 weeks of abstinence, and the emergence of impaired behavioral restraint (increased false alarms) at 7 weeks of abstinence. Collectively, these findings demonstrate the emergence of increased impulsive action in alcohol-dependent rats during protracted alcohol abstinence and suggest the 5C-CPT with visual distractors may provide a viable behavioral platform for characterizing the neurobiological substrates underlying impaired behavioral inhibition resulting from chronic intermittent alcohol exposure.

Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade

“…Importantly, a recent meta‐analysis reported significantly decreased recruitment of the salience network during inhibitory control tasks in 30 reviewed studies investigating response inhibition in addicted individuals . This finding parallels reports of increased measures of impulsivity in rodents with a history of chronic alcohol exposure . Besides decreased connectivity within the salience network, we also observed increased coupling between constituents of the salience and the reward system in PD rats.…”

Conflict anticipation in alcohol dependence — A model-based fMRI study of stop signal task

“…In rodent models, rats under chronic intermittent alcohol exposure exhibited deficits in impulsive control in a five-choice continuous performance task (Irimia et al, 2014). Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol seeking behavior in adulthood (Gass et al, 2014).…”

Sex differences in adolescent ethanol drinking to behavioral intoxication

“…The increase in impulsive action was only evident following abstinence, which may suggest that adaptations occur during abstinence that may lead to this change in the behavioral response to ethanol. Abstinence from chronic intermittent ethanol exposure in adult male rats leads to neural (Irimia, Buczynski, Natividad, Laredo, Avalos, & Parsons, 2017) and behavioral adaptations (Irimia, Tuong, Quach, & Parsons, 2014;Irimia et al, 2017), including increased premature responding, without re-exposure to ethanol. In the present study, we measured premature responding after resumption of ethanol drinking following abstinence, but did not measure premature responding during abstinence.…”