Brain monoamines in the rhesus monkey during long-term neuroleptic administration

1. In this study, rhesus monkeys were given daly high doses of chlorpromazine (up to 40 mg/kg orally) or haloperidol (up to 1 mg/kg orally) for up to 17 months. After sacrifice the brains were analyzed for regional concentrations of DA, HVA, 5-HT, 5-HIAA, and NE. 2. The most prominent effects of this long-term administration of neuroleptics were (a) a widespread elevation of NE levels in the forebrain, including the hypothalamus, thalamus, olfactory area, and nucleus accumbens; (b) a decrease of 5-HT turnover (calculated from the ratio "5-HT/5-HIAA") in several limbic forebrain areas, including the amygdaloid nucleus, septum, and nucleus accumbens as well as thalamus; and (c) a mild but consistent increase of HVA concentration in all DA-containing forebrain regions; in the striatum, this effect was found in the CPZ but not the HAL group. 3. The possible involvement of these neurochemical changes in the clinical actions of neuroleptics characteristically requiring long-term medication, such as the production of persistent (tardive) dyskinesias as well as the antipsychotic effect, is discussed.