A central 6-hydroxydopamine lesion prevents fluphenazine-induced increase in plasma homovanillic acid.

Plasma and brain levels of the dopamine metabolite, homovanillic acid, were measured in rats after acute and chronic treatment with fluphenazine. After acute administration, homovanillic acid levels were increased in the whole frontal cortex, caudate nucleus, nucleus accumbens, anterior cingulate (supragenual) cortex, prefrontal cortex and plasma. Following chronic administration, the effects of single doses of fluphenazine in increasing homovanillic acid were markedly attenuated in the caudate nucleus, nucleus accumbens, the whole frontal cortex, anterior cigulate cortex and plasma, but not in the prefrontal (anteromedial) cortex. Following fluphenazine administration plasma homovanillic acid levels were correlated with homovanillic acid concentrations in whole frontal cortex (r = 0.63, p less than 0.01) and caudate nucleus (r = 0.51, p less than 0.05). Further, prior intracerebroventricular administration of 6-hydroxydopamine prevented the fluphenazine-induced increase in plasma homovanillic acid. These data suggest that in the rat, plasma and brain (caudate nucleus and whole frontal cortex) homovanillic acid levels change in a similar fashion during acute and chronic neuroleptic administration.