Effect of chronic haloperidol on dopamine release following microinjection of GABA into the substantia nigra zona reticulata in the rat.

To investigate the influence of the striatonigral gamma-aminobutyric acid (GABA) system on the nigrostriatal dopamine (DA) system, the release of DA and/or 3,4-dihydroxyphenylacetic acid in the striatum ipsilateral to the injection side was examined by in vivo voltammetry following microinjection of GABA into the substantia nigra zona reticulata (SNR). The microinjection of GABA (100-300 micrograms/2 microliters) into the SNR produced a dose-dependent increase in the electrochemical signals recorded from the caudate nucleus ipsilateral to the injection side. Following chronic treatment with haloperidol, microinjection of GABA into the SNR produced only a slight (non-significant) increase in the electrochemical signals recorded from the caudate nucleus ipsilateral to the injection side. These results provide additional evidence to support the concept that DA cells in the substantia nigra zona compacta are regulated by the SNR non-DA neurons in an inhibitory manner. It appears, furthermore, that chronic treatment with haloperidol reduces the release of DA in the striatum ipsilateral to the injection side and that this effect may be due to a gradual development of depolarization block of DA cells by chronic administration of haloperidol.