DOUBLE DISSOCIATION OF THE EFFECTS OF HALOPERIDOL AND THE DOPAMINE D3 RECEPTOR-SPECIFIC ANTAGONIST ABT-127 ON ACQUISITION VS. EXPRESSION OF COCAINE CONDITIONED ACTIVITY
Banasikowski, Tomek J.
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The psychostimulant effects of cocaine can be associated with environmental stimuli and thus can be easily conditioned in a laboratory setting. In rats, both behavioural stimulant and reinforcing effects of cocaine have been induced by presentation of stimuli previously paired with cocaine treatment. The stimulant locomotor response evoked by contextual stimuli is termed conditioned activity. It is hypothesized that haloperidol and the specific D3 receptor antagonist ABT-127 will produce a doubly dissociable effect on acquisition vs. expression of cocaine conditioned activity. Male rats received three 1-hr sessions of habituation to activity monitoring chambers (outfitted with infrared emitters and detectors), one session each day, over 3 days during which no drug was administered. The conditioning phase began on the next day and consisted of three 1-hr sessions, one every 48 hrs. Rats were pre-treated intraperitoneally (IP) with haloperidol (50 µg/kg) or ABT-127 (1 mg/kg) (or vehicle) 1 hr and 0.5 hr before being placed into the activity chambers, respectively, and with the indirect-acting dopamine agonist cocaine (10 mg/kg) or saline immediately before placement into the chambers. The expression phase took place 48 hrs following the last conditioning session. Animals received a single injection of haloperidol, ABT-127 (or vehicle) 1 hr or 0.5 hr prior to placement in the activity chambers and saline was administered immediately before. Analyses revealed a significant interaction of drug by phase. In agreement with my hypothesis, haloperidol given during the conditioning phase blocked the acquisition of conditioned activity but failed to block the expression of conditioning when given on the test day. In contrast, ABT-127, when given before cocaine during conditioning failed to block the acquisition of conditioned activity but blocked the expression of conditioning when administered on the test day. Results suggest that D2 receptors are necessary for acquisition but not initial expression and D3 receptors are required for expression but not acquisition of cocaine conditioned activity.