Selective Effects of Low-Dose D₂ Dopamine Receptor Antagonism in a Reaction-Time Task in Rats

Abstract

Operant responses involving a cued discrimination are sensitively disrupted by neuroleptic drugs that block dopamine (DA) receptors in the brain; however, it is not clear which DA receptor subtypes may be involved in these effects. The role of D₁ or D₂ DA receptor antogonists on the execution of a conditioned reaction-time (RT) motor task was investigated in the present study. Rats were trained to release a lever after the presentation of a visual cue within a RT limit to be reinforced by a food pellet. The D₁ receptor antagonist SCH-23390, at doses that significantly decrease the behavioral effects of cocaine, did not impair performance at any dose (5, 10, or 20 μg/kg) injected subcutaneously. In contrast, a selective D₂ receptor antagonist raclopride (50, 100, or 200 μg/kg) induced a dose-dependent increase in the number of incorrect responses (release of the lever over the RT limit) associated with an increase in the RT. The results suggest that the dopaminergic nigrostriatal system, which has previously been shown to be specifically involved in this RT task (Amalric and Koob 1987), appears to be a sensitive site for sensorimotor integration, and that the execution of the conditioned RT motor task may depend preferentially on the activation of the dopaminergic D₂ receptors in this system.