Pimozide prevents the response-reinstating effects of water reinforcement in rats.

Thirsty animals were trained to traverse a straight runway once each day for a reward consisting of 100 licks from a water-filled drinking tube. Once running speeds had stabilized, single daily extinction trials were initiated during which no water reinforcement was provided in the goal box. Extinction trials continued until running had slowed to levels approximately half of that observed during reinforced trials. A single treatment trial was then conducted in which some animals found water in the goal box and others continued to find an empty water bottle. Those subjects that were reinforced on treatment day subsequently demonstrated a reinstatement of their operant running response on the very next trial (i.e., 24 hr later). However, pretreatment with 1.0 mg/kg (but not 0.5 mg/kg) of the dopamine antagonist drug, pimozide, attenuated this response-reinstating effect of water-reinforcement. This action of pimozide was not likely a consequence of some residual sedative or motor incapacitation since a) the test day was conducted 24 hr after the treatment day by which time the pharmacological actions of the drug had greatly subsided; b) a Motor Control group administered pimozide after the reinforced trial exhibited normal response-reinstatement 24 hr later on Test Day; and c) on treatment day, pimozide did not reliably attenuate running times, latency to initiate drinking, nor the rate of licking behavior. Together, these data suggest that dopamine receptor antagonism can produce an attenuation in the reinforcing efficacy of water.