Impulsive action in the 5-choice serial reaction time test in 5-HT₂c receptor null mutant mice.

RATIONALE: Depletion of brain serotonin (5-HT) results in impulsive behaviour as measured by increased premature responding in the five-choice serial reaction time (5-CSRT) test. Acute selective blockade of 5-HT2C receptors also increases this form of impulsive action, whereas 5-HT2C receptor stimulation reduces premature responding.

OBJECTIVES

These experiments determined the impact of genetic disruption of 5-HT2C receptor function on impulsive responding in the 5-CSRT test.

METHODS

Food-restricted 5-HT2C receptor null mutant and wild-type (WT) mice were trained on the 5-CSRT test in which subjects detect and correctly respond to brief light stimuli for food reinforcement. Impulsivity is measured as premature responses that occur prior to stimulus presentation.

RESULTS

Both lines of mice quickly learned this task, but there were no genotype differences in premature responding or any other aspect of performance. A series of drug challenges were then given. The 5-HT2C receptor agonist Ro60-0175 (0.6 mg/kg) reduced premature responding in WT mice but not mutant mice. The 5-HT2C receptor antagonist SB242084 increased premature responding in WT mice only. Cocaine increased premature responding at 7.5 mg/kg but not at a higher dose that disrupted overall responding; these effects were observed in both lines of mice. Amphetamine (0.25 and 0.5 mg/kg) did not affect premature responding, but disrupted other aspects of performance in both genotypes.

CONCLUSIONS

Genetic deletion of 5-HT2C receptor function does not induce an impulsive state or exacerbate that state induced by psychomotor stimulants but does prevent the acute effects of 5-HT2C receptor stimulation or blockade on impulsive action.