Effects of atypical antipsychotic drugs on dopamine output in the shell and core of the nucleus accumbens: role of 5-HT(2A) and alpha(1)-adrenoceptor antagonism.
The effects of acute intravenous administration of several new, atypical antipsychotic 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-HT(2A) receptor 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 examined in the two subdivisions of the nucleus accumbens (NAC), the core and shell, which seem associated with motor control and limbic functions, respectively, by using in vivo differential normal pulse voltammetry in anaesthetised, pargyline-pretreated rats. Both quetiapine and sertindole, in the two doses used, caused a more pronounced dopamine release in the shell than in the 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 high dose increased dopamine output to a greater extent in the core. M100907 selectively increased dopamine output in the shell. Also, prazosin significantly increased dopamine output in the shell, but not in the core. The results indicate that both 5-HT(2A) and alpha(1)-adrenoceptor antagonism may play an important role in the preferential effect of atypical APDs on dopamine output in the shell versus the core of the NAC.
Marcus
M M
MM
Section of Neuropsychopharmacology, Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77, Stockholm, Sweden.
Nomikos
G G
GG
Svensson
T H
TH
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003987:Dibenzothiazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005464:Fluorobenzenes / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D000077152:Olanzapine; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D018674:Adrenergic Antagonists; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D005464:Fluorobenzenes; D007093:Imidazoles; D007211:Indoles; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D010890:Pirenzepine; C079049:volinanserin; C066304:sertindole; D000077152:Olanzapine; D004298:Dopamine