Evidence for a role of 5-HT^sub 2C^ receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule

5-Hydroxytryptamine^sub 2C^ (5-HT^sub 2C^) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment. Mathematical models can help to differentiate between these processes. The effects of the 5-HT^sub 2C^ receptor agonist Ro-600175 (([alpha]S)-6-chloro-5-fluoro-[alpha]-methyl-1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m-chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio schedule maintained by food pellet reinforcers were assessed using a model derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of schedule-controlled behavior, 'mathematical principles of reinforcement'. Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analyzed using the model. The effects of the agonists on estimates of the model's parameters, and the sensitivity of these effects to selective antagonists, were examined. Ro-600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a (the parameter expressing incentive value), but both agonists increased δ (the parameter expressing minimum response time). The effects of both agonists could be attenuated by the selective 5-HT^sub 2C^ receptor antagonist SB-242084 (6-chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1-carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5-HT^sub 1B^ receptor antagonist, or MDL-100907 ((±)2,3-dimethoxyphenyl-1-(2-(4-piperidine)methanol)), a selective 5-HT^sub 2A^ receptor antagonist. The results are consistent with the hypothesis that the effect of the 5-HT^sub 2C^ receptor agonists on progressive ratio schedule performance is mediated by an impairment of motor capacity rather than by a reduction of the incentive value of the food reinforcer.