Differential actions of typical and atypical antipsychotic drugs on dopamine release in the core and shell of the nucleus accumbens.
The effects of acute administration of typical and atypical antipsychotic drugs on extracellular dopamine (DA) concentrations in brain were examined in two subdivisions of the nucleus accumbens (NAC), the core and the shell, which are largely associated with motor control and limbic functions, respectively, by using in vivo differential normal pulse voltammetry in anesthetized, pargyline pretreated rats. The following drugs were studied: haloperidol (0.1 and 1.0 mg/kg), clozapine (1.0 and 5.0 mg/kg), amperozide (1.0 and 2.0 mg/kg), risperidone (0.1 and 1.0 mg/kg), the selective 5-HT2A/5-HT2C receptor antagonist ritanserin (1 mg/kg) and the selective DA-D2/D3 receptor antagonist raclopride (10 and 320 micrograms/kg). Drugs with predominantly high 5-HT2 receptor antagonistic action, such as amperozide and ritanserin, as well as low doses of either risperidone or clozapine increased DA concentrations to a greater extent in the shell than in the core subdivision of the NAC. In contrast, drugs with a more potent D2 receptor antagonistic action, such as haloperidol and raclopride, as well as high doses of either risperidone or clozapine, elicited a larger DA increase in the core than in the shell. Consequently, atypical antipsychotics characterized by potent 5-HT2 receptor antagonism can be differentiated from typical antipsychotic drugs on the basis of their preferential effect on DA transmission in the shell region of the NAC.
Marcus
M M
MM
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nomikos
G G
GG
Svensson
T H
TH
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D004298:Dopamine