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.
Highlights
Alcohol dependence is associated with significant disruptions in executive functions [1,2] which likely contribute to the loss of control and relapse that characterize alcohol addiction [3]
The 5C-Continuous Performance Task (CPT) allows the evaluation of chronic alcohol effects on two different types of impulsive behaviors; the inability to wait for a stimulus presentation and the inability to restrain a prepotent response when presented with a NoGo stimulus
EtOH intake of 8.7360.2 g/kg/day resulting in 210614 mg% blood alcohol levels). 5 ChoiceContinuous Performance Task (5C-CPT) evaluations were performed during a subsequent 7-week abstinence period with visual distractor ‘‘challenge’’ tests performed during the 3rd, 5th and 7th week of abstinence to increase task difficulty in an effort to unveil EtOH-related cognitive impairment
Summary
Alcohol dependence is associated with significant disruptions in executive functions [1,2] which likely contribute to the loss of control and relapse that characterize alcohol addiction [3]. The 5-CSRTT does not incorporate NoGo trials and in this respect these studies do not fully generalize to clinical research studies reporting deficits in the capacity to inhibit prepotent motor responses by alcoholics To address this the present experiments employed a recently developed rodent version of the CPT, the 5 Choice-CPT (5CCPT) [32,33], that incorporates random presentation of NoGo trials throughout a succession of rapidly presented Go trials. The 5C-CPT allows the evaluation of chronic alcohol effects on two different types of impulsive behaviors; the inability to wait for a stimulus presentation (impulsive action; indexed by premature responses) and the inability to restrain a prepotent response when presented with a NoGo stimulus (impaired behavioral inhibition or behavioral restraint; indexed by false alarm responses). Toward this goal separate groups of rats were trained in the 5C-CPT, given chronic intermittent access to either an EtOH-containing or EtOH-free liquid diet, further probed in the 5C-CPT during abstinence periods ranging from 3 hours to 7 weeks
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