Conditioned aversive responses produced by delayed, but not immediate, exposure to cocaine in male Sprague-Dawley rats

Abstract

Cocaine abuse is accompanied by the emergence of negative affect such as dysphoria irritability and anhedonia. Cues associated with cocaine are rapidly learned by animals and are capable of eliciting a negative affective state that can trigger relapse, indicating a critical role for associative mechanisms in the regulation of drug seeking. Using the taste reactivity test, the conditions under which a taste paired with delayed cocaine is able to elicit a conditionally aversive state was examined. It is demonstrated that delayed cocaine produces conditioned gaping when saccharin is paired with either a 10- or 30-min delay, whereas immediate cocaine does not result in aversive behaviours. Morphine also produces conditioned gaping in the 10 min procedure. Rats who received delayed cocaine-paired saccharin exhibit increased anxiety-like behaviours. Saccharin needed to be administered intermittently throughout the delay in order to produce the conditioned aversive state. Pre-treatment with ondansetron, SCH 23390 or OlGly interfered with the establishment of conditioned gaping to saccharin paired with delayed cocaine, but only during early trials.