Effects of acute and subchronic administration of typical and atypical antipsychotic drugs on the neurotensin system of the rat brain.

The acute and subchronic effects of a variety of doses of a prototype typical (haloperidol) or one of several atypical antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine, or sertindole) on regional brain neurotensin (NT) tissue concentrations, and NT receptor binding were examined. Acute administration of haloperidol, clozapine, olanzapine, and risperidone dose-dependently increased NT tissue concentrations in the nucleus accumbens. Haloperidol, olanzapine, risperidone, and sertindole also increased NT tissue concentrations in the caudate nucleus. NT tissue concentrations in the nucleus accumbens and caudate remained elevated after 14-day administration of haloperidol, olanzapine, sertindole, and risperidone. In contrast, at the doses studied, quetiapine decreased NT tissue concentrations in the nucleus accumbens; clozapine had no effect. Haloperidol significantly increased NT receptor binding in the substantia nigra after 14-day administration. All of the atypical antipsychotic drugs decreased NT receptor binding in the nucleus accumbens and in the substantia nigra. Although these studies do not conclusively support the hypothesis that increased NT neurotransmission is involved in the clinically relevant effects of all antipsychotic drugs, the extant evidence clearly suggests that further study is warranted. Inconsistencies in the data suggest that differential effects of antipsychotic drug administration on subpopulations of NT neurons must be scrutinized further.