Effect of nigral lesion on chlorpromazine-induced acceleration of dopamine synthesis from [14C]tyrosine

Abstract

The nigro-neostriatal dopamine pathway of the rat brain was subjected to a unilateral stereotaxic lesion at the level of the hypothalamic-mesencephalic junction. Fifteen days after the operation endogenous dopamine and[14C]dopamine formed in vivo from [14C]tyrosine were reduced to about 15% in the striatum ipsilateral to the lesion. Twenty-four h after the lesion the contents of endogenous and labelled dopamine were about the same in the striata of both sides. Chlorpromazine (15 mg/kg) accelerated several fold the accumulation of [14C]dopamine formed from [14C]tyrosine in the striatum on the intact side. However, in the striatum on the side of the lesion, chlorpromazine did not increase the accumulation of [14C]dopamine. The results indicate that chlorpromazine accelerates dopamine synthesis in the striatum by an indirect mechanism, presumably by activating the nerve impulse flow in the nigro-neostriatal dopamine pathway.