Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule

Rationale 5-Hydroxytryptamine 2C (5-HT 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. Objective The effects of the 5-HT 2C receptor agonist Ro-600175 ((α S )-6-chloro-5-fluoro-α-methyl-1 H -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 behaviour, ‘mathematical principles of reinforcement’. Method Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analysed 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. Results 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 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 1B receptor antagonist, or MDL-100907 ((±)2,3-dimethoxyphenyl-1-(2-(4-piperidine)methanol)), a selective 5-HT 2A receptor antagonist. Conclusions The results are consistent with the hypothesis that the effect of the 5-HT 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.