Alterations in dopamine metabolism after chronic administration of haloperidol. Possible role of increased autoreceptor sensitivity.

Basal levels of the metabolites of dopamine (DA) were reduced following the chronic administration of haloperidol. The ability of small doses (50 or 100 micrograms/kg) of apomorphine to reduce the concentrations of the metabolite of DA, homovanillic acid (HVA), was also enhanced following the chronic administration of haloperidol. In addition, the accumulation of DA and of the metabolite of DA, 3-methoxytyramine (3-MT), in rats treated with pargyline was reduced following the chronic administration of haloperidol, suggesting that basal turnover and release of DA also may be reduced. These findings are discussed in relation to possible changes in the sensitivity of DA autoreceptors and the activity of DA-containing neurons.