Drug discrimination in rats: evidence for amphetamine-like cue state following chronic haloperidol

Two groups of male Sprague-Dawley rats were trained to discriminate which of two levers to press for milk reinforcement on a VI-20 sec schedule of reinforcement on the basis of whether they were injected intraperitoneally with d-amphetamine (0.50 mg/kg or 1.50 mg/kg) or saline 15 min prior to daily 30 min training sessions. Following acquisition of the discrimination, dose-response functions were generated for both training-dose groups during 5 min test sessions. All subjects were then injected with 1.0 mg/kg of haloperidol for ten consecutive days and retested on either saline or intermediate doses of amphetamine on days 1, 2, 4 and 7 following the final haloperidol injection. The results indicated that chronic haloperidol enhanced the discriminative stimulus properties of amphetamine in both training groups. More importantly, when tested on saline, subjects in both training groups made significantly more responses on the d-amphetamine lever than observed prior to chronic haloperidol. On the basis of linear regression analysis of the dose-response curves it was shown that rats in both groups responded as though they had been injected with 0.18 mg/kg of d-amphetamine. In a second experiment this increase in amphetamine-lever responding when animals were tested with saline following chronic haloperidol was replicated and in addition it was observed that chronic amphetamine had the opposite effect on this measure.