Activation of 5-HT2A receptors impairs response control of rats in a five-choice serial reaction time task

The present experiments investigated the effects of agents acting at seroto nin (5-HT)-(2) receptors on the performance of rats in a choice serial reac tion time (5-CSRT) task in order to examine the role of 5-HT2 receptors in the modulation of attention and response control. The results indicate that DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride; 0 .05, 0.1 and 0.2 mg/kg, subcutaneously], a 5-HT2A/2C agonist, slightly impa ired the choice accuracy of the well performing rats and markedly increased their premature responding. DOI (0.05 and 0.1 mg/kg) had no effect on the latency to collect earned food pellets or to respond correctly, indicating that these lower doses of DOI did not reduce motivation for the food reward in this task. The selective effect of a low dose of DOI (0.1 mg/kg) on pre mature responding was completely blocked by ketanserin (0.2 mg/kg), a 5-HT2 A/2C antagonist, and ritanserin (0.3 mg/kg), a 5-HT2A/2C antagonist, but on ly partially blocked by a high dose of SER082 (1.0 mg/kg), a 5-HT2C antagon ist. In contrast to DOI, mCPP, [1-(3-phenyl)piperazine; 0.05 and 0.15 mg/kg ], a 5-HT2C agonist, had no effect on choice accuracy or premature respondi ng, but it reduced behavioral activity and/or arousal as indicated by the d ecreased number of trials completed and increased the probability of omissi ons. SER082 (1.0 mg/kg) blocked the effects of mCPP on performance. These d ata suggest that the overactivation of 5-HT2A receptors impairs response co ntrol in a 5-CSRT task, whereas the overactivation of 5-HT2C receptors can affect behavioral activity and/or arousal state of the animals for this foo d rewarded task. (C) 2000 Elsevier Science Ltd. All rights reserved.