Disruption of conditioned reaction time performance by dopamine receptor antagonists in the rat

The effects of the neuroleptics haloperidol, cis-flupenthixol and chlorpromazine, and the selective dopamine (DA) receptor antagonists raclopride and SCH 23390, were assessed in a conditioned reaction time task. In this operant task, rats were required to hold down a lever for a randomly determined hold duration (0.5-2.0s) and to release the lever within 1s of a light cue to obtain food reinforcement. All drugs dose-dependently reduced the total number of lever presses and the number of rewarded responses, and all but chlorpromazine produced an abrupt cessation of responding before the end of the experimental session. However, there were variations in the ability of these drugs to impair lever release performance. Chlorpromazine and the selective D2 antagonist raclopride significantly elevated rewarded and total reaction times. The former drug also increased the number of delayed responses (i.e. those occurring with a latency of greater than 1s) and reduced the percentage of rewarded responses occurring following light onset (percentage success), whilst raclopride also increased delayed reaction times. Haloperidol failed significantly to influence rewarded and total reaction times, as well as the percentage success measure. However, the lowest dose of haloperidol increased the number of delayed responses, indicating a subtle impairment of lever release performance. cis-Flupenthixol and the selective D1 antagonist SCH 23390 failed significantly to influence any aspect of lever release performance. Only haloperidol and cis-flupenthixol increased the time rats took to move from the lever to the food hopper, whilst all drugs increased the time taken to return to the lever. Although feeding animals prior to the experimental session, or removing food pellets from the dispensers during the session, reduced overall response levels, the former did not influence any reaction time measure, whilst extinction only reduced percentage success. The present findings reveal that certain DA receptor antagonists impair conditioned lever release performance. However, this reaction time deficit is not obtained with all DA receptor antagonists, despite their consistent effects on other aspects of performance in the task.