Regionally specific effects of atypical antipsychotic drugs on striatal Fos expression: The nucleus accumbens shell as a locus of antipsychotic action.
The mechanisms by which atypical antipsychotic drugs such as clozapine exert therapeutic effects but do not induce extrapyramidal side effects are not clear. We have examined the effects of acute administration of three antipsychotic drugs on Fos protein expression in the striatal complex. The ypical neuroleptic haloperidol was compared with the atypical agent clozapine and the putative atypical antipsychotic drug remoxipride. Haloperidol increased the number of neurons expressing Fos-like immunoreactivity in both the dorsolateral and the medial striatum and increased Fos expression in the nucleus accumbens core and shell. Clozapine increased Fos in the nucleus accumbens shell, but not in the core or two neostriatal sectors. Remoxipride significantly increased the number of Fos-like immunoreactive neurons in the medial but not the dorsolateral striatum, and increased the number of cells expressing Fos protein in the nucleus accumbens shell but not core. The remoxipride-induced increase in the number of medial striatal neurons expressing Fos was entirely attributable to a selective increase in the striatal patch compartment, whereas haloperidol increased Fos protein in neurons of both striatal compartments. These data indicate that typical and atypical antipsychotic drugs exert regionally distinct effects on striatal Fos expression, and suggest that the dorsolateral striatum may be a locus involved in the genesis of extrapyramidal side effects. All three antipsychotic drugs increased Fos expression in the shell of the nucleus accumbens. The shell of the nucleus accumbens may be a site of antipsychotic action.
Deutch
A Y
AY
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA; Department of Veterans Affairs Medical Center, West Haven, Connecticut 06516, USA.
Lee
M C
MC
Iadarola
M J
MJ