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 (impulsive) responding induced by DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride], a 5-HT2A/2C receptor agonist, is mediated by activation of the dopaminergic system and if this effect of DOI occurs in the nucleus accumbens. Therefore, the effects of a dopamine (D-1/2) receptor antagonist given alone or combined with DOI were examined on the performance of rats in a five-choice serial reaction time (5-CSRT) task. Secondly, the effects of DOI in nucleus accumbens core and shell were studied, in order to find the target brain area for DOI-induced premature responding. The results indicate that DOI (0.1 mg/kg, subcutaneously) increases the number of premature 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 receptor antagonist, attenuated the DOI-induced enhancement in premature responding. SCH 23390 (0.005 mg/kg), a selective D-1 receptor antagonist with little 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 injections 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 effect 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.