Studies on the involvement of the dopaminergic system in the 5-HT2 agonist(DOI)-induced premature responding in a five-choice serial reaction time task

The present experiments investigated whether the enhanced premature (impuls ive) responding induced by DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-ami nopropane hydrochloride], a 5-HT2A/2C receptor agonist, is mediated by acti vation of the dopaminergic system and if this effect of DOI occurs in the n ucleus accumbens. Therefore, the effects of a dopamine (D-1/2) receptor ant agonist given alone or combined with DOI were examined on the performance o f rats in a five-choice serial reaction time (5-CSRT) task. Secondly, the e ffects of DOI in nucleus accumbens core and shell were studied, in order to find the target brain area for DOI-induced premature responding. The resul ts indicate that DOI (0.1 mg/kg, subcutaneously) increases the number of pr emature responses, as found previously, alpha -Flupenthixol (0.03 mg/kg), a D-1/2 dopamine receptor antagonist, and raclopride (0.015 mg/kg), a D-2 re ceptor antagonist, attenuated the DOI-induced enhancement in premature resp onding. SCH 23390 (0.005 mg/kg), a selective D-1 receptor antagonist with l ittle affinity to 5-HT2 receptors totally blocked the effect of DOI. Those doses of DA antagonists did not significantly decrease premature responding when given alone. On the other hand, higher doses of all of these dopamine antagonists increased the number of omissions and decreased the number of ITI hole responses. In contrast to subcutaneous administration, direct inje ctions of DOI (1, 3, and 10 mug bilaterally) to the nucleus accumbens shell or core had no effect on premature responding. These results suggest that the activation of the dopamine system mediates, at least in part, the effec t of a 5-HT2 agonist on premature responding, but the nucleus accumbens is not the primary site for this action. (C) 2001 Elsevier Science Inc.