Medial prefrontal cortical D2 and striatolimbic D4 dopamine receptors: common targets for typical and atypical antipsychotic drugs.
1. In vitro receptor autoradiography was used to examine the long-term effects of a typical (fluphenazine), atypical (clozapine), or potential atypical antipsychotic (S[+]-N-n-propylnorapomorphine; [+]-NPA) on different dopamine (DA) receptor subtypes. 2. D1-Like and D3 receptor levels were not changed with any treatment in any brain region examined. 3. D2 Receptors in caudate-putamen (CPu), nucleus accumbens (NAc) and olfactory tubercle (OT) were significantly increased by long-term treatment with fluphenazine, but not with clozapine or S[+]-NPA. 4. D2 Receptor levels in medial prefrontal cortex (MPC), but not dorsolateral frontal cortex (DFC), were elevated after repeated daily administration of fluphenazine, clozapine, and S[+]-NPA. 5. D4-Like receptors, assayed under D4-selective conditions, were increased by fluphenazine, clozapine and S(+)-NPA in both NAc and CPu, but by none of these treatments in OT, DFC or MPC. 6. These results support a common role for medial prefrontal cortical D2 and striatolimbic D4 receptors in mediating the clinical actions of typical and atypical antipsychotic drugs.
Tarazi
F I
FI
Consolidated Department of Psychiatry & Neuroscience Program, Harvard Medical School, Belmont, MA, USA.
Yeghiayan
S K
SK
Neumeyer
J L
JL
Baldessarini
R J
RJ
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D066298:In Vitro Techniques; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D014793:Visual Cortex / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine