Discriminative stimulus properties of haloperidol

Rats (N = 9) were trained to discriminate the antipsychotic drug haloperidol (0.05 mg/kg i.p.) from drug vehicle (0.25% acetic acid in 0.9% saline) using a water‐reinforced, fixed‐ratio 10 response operant procedure. Acquisition of discrimination required a mean of 45 trainingsessions (median value of 38 sessions). The discriminative stimulus was dose‐dependent with an ED₅₀ value of 0.008 mg/kg. The total number of responses per 10‐min test session was significantly reduced at all doses of haloperidol that produced haloperidol lever selection. The antipsychotic drug chlorpromazine substituted for the haloperidol discriminative stimulus (ED₅₀ = 0.38 mg/kg). The indirect dopaminergic agonists amphetamine (1.0 mg/kg) and cocaine (10 mg/kg) fully blocked the haloperidol discriminative stimulus. Taken together, these initial results suggest that the discriminative stimulus produced by haloperidol is mediated, at least in part, by an interaction with dopamine receptors.