Haloperidol prevents the reinstatement of amphetamine-rewarded runway responding in rats.

Animals were trained to traverse a straight-alley once each day for a reward of 1.0 mg/kg SC d-amphetamine sulfate. After 14 days of acquisition, extinction trials were initiated in which the amphetamine reward was replaced by injections of physiological saline. After running speeds had decreased to less than one third those of preextinction values, rats received a single amphetamine-rewarded trial either in the absence or presence of haloperidol (0.075, 0.15 or 0.3 mg/kg IP). Twenty-four hours later, animals were tested for reinstatement of operant running in a single drug-free Test trial. Animals that were nondrugged during the amphetamine-rewarded trial demonstrated a statistically reliable increase in running speed on the Test trial relative to extinction baseline speeds. In contrast, animals that were under the influence of medium or high doses of haloperidol during the amphetamine-rewarded trial failed to show Test day increases in running speed. This result did not stem from some residual sedative or performance impairing quality of the drug since a "motor control group" administered a high dose of haloperidol shortly after a rewarded trial, was able to demonstrate unimpaired reinstatement of operant running on Test day (i.e., 24 hr later). These findings support the view that dopamine systems play a role in the neural substrates underlying the incentive motivational properties of amphetamine reinforcement.