Modification of avoidance responding by amphetamine and dopamine receptor antagonists

This study was designed to investigate the effects of preferential D1 (SCH 23390) and D2 (haloperidol) dopamine (DA) receptor antagonists and their interaction with low-dose (1 mg kg) D-amphetamine during the acquisition of two-way shuttle avoidance in rats. In the course of training, the dissociation of drug effects on response latencies was observed. Haloperidol (0.05 mg/kg) caused significant reduction in the frequency of short-latency avoidance responses that was only partially compensated by concomitant amphetamine administration. In contrast, SCH 2339 (0.025 mg/kg) did not affect the frequency of short-latency responses but lowered probability of avoidances emitted toward the end of 5 s interval between the onsets of conditoned and unconditioned stimuli (CS-UCS interval). Amphetamine compensated for this impairment by increasing frequency of short-latency avoidances well above the control level. These results argue for different nature of short- and long-latency avoidance responses, and suggest involvement of DA D2 receptors in the process of response initiation facilitated by amphetamine. Interestingly, a profound behavioral breakdown was observed under higher dose of SCH 23390 (0.05 mg/kg), but only when applied together with amphetamine. The latter result seems to confirm the notion that behavioral output of dopaminergic transmission may depend more on the balance between D1 and D2 receptors than on the independent modulation of particular receptor system.