Increase of dopamine turnover in bilateral striata after unilateral injection of haloperidol into substantia nigra of unrestrained rats.

In order to investigate self-regulation of dopamine (DA) neurons, the effects of intranigrally administered haloperidol (Hal), a DA receptor antagonist, on nigrostriatal DA systems were examined using differential pulse voltammetry with carbon fiber electrode. The measurements were achieved in the bilateral caudate-putamen (CP) of behaving rats, in the region of which DA or 3,4-dihydroxyphenylacetic acid made an oxidative current peak (P 2 ) spontaneously. Unilateral injection of Hal (5 μg in 1 μl) into the substantia nigra of rat increased P 2 in a time-dependent manner. This phenomenon was observed in both CP, but a more significant increase was in the ipsilateral side (156 ± 2% of spontaneous height 2.75 h after injection) than in the contralateral side (129 ± 7%). These effects enlarged in a dose-dependent manner. The same results were found in tissue homogenates determined by high-performance liquid chromatography with electrochemical detection. In the latter case, however, no significant difference was observed between the left and right sides. The present results suggest that Hal, attaching nigral autoreceptors on the cell bodies and dendrites, blocks inhibitory influence of endogenous DA and then activates the nigrostriatal DA neurons, while the contribution of non-dopaminergic neurons is also possible.