Effects of atypical antipsychotic drugs on dopamine output in the shell and core of the nucleus accumbens: role of 5-HT2A and alpha(1)-adrenoceptor antagonism

The effects of acute intravenous administration of several new, atypical an tipsychotic drugs (APDs): olanzapine (0.05 and 1.0 mg/kg), sertindole (0.1 and 1.0 mg/kg) and quetiapine (0.25 and 2.5 mg/kg), a selective 5-HT2A rece ptor antagonist, M100907 (0.03 and 0.3 mg/kg), and an alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg), on regional dopamine output were examine d in the two subdivisions of the nucleus accumbens (NAC), the core and shel l, which seem associated with motor control and limbic functions, respectiv ely, by using in vivo differential normal pulse voltammetry in anaesthetise d, pargyline-pretreated rats. Both quetiapine and sertindole, in the two do ses used, caused a more pronounced dopamine release in the shell than in th e core region of the NAC. In contrast, the low dose of olanzapine increased dopamine output almost to the same extent in both regions, whereas the hig h dose increased dopamine output to a greater extent in the core. M100907 s electively increased dopamine output in the shell. Also, prazosin significa ntly increased dopamine output in the shell, but not in the core. The resul ts indicate that both 5-HT2A and alpha(1)-adrenoceptor antagonism may play an important role in the preferential effect of atypical APDs on dopamine o utput in the shell versus the core of the NAC. (C) 2000 Elsevier Science B. V. All rights reserved.