Intrastriatal GABA A receptor blockade does not alter dopamine D 1/D 2 receptor interactions in the intact rat striatum

Abstract

The purpose of this study was to investigate the effects of intrastriatal blockade of GABA A receptors on dopamine D 1/D 2 receptor interactions in the intact rat striatum. Muscarinic receptors mediate the ability of the D 2 receptor antagonist, eticlopride, to block an increase in striatonigral neuropeptide messenger RNA stimulated by the full D 1 agonist, SKF-82958. However, because D 2 receptor antagonists activate striatopallidal neurons, it is possible that increased GABA release from local medium spiny axon collaterals also contributes to the ability of eticlopride to block the effects of SKF-82958. This hypothesis was addressed by infusing the GABA A receptor antagonist, bicuculline, into the dorsal striatum in rats treated with eticlopride and SKF-82958. In contrast to the actions of the muscarinic antagonist, scopolamine, bicuculline did not affect the increase in behaviors induced by SKF-82958 or the ability of eticlopride to block them. Quantitative in situ hybridization demonstrated that bicuculline did not significantly affect basal preprodynorphin messenger RNA, nor did it affect the ability of eticlopride to decrease SKF-82958-induced preprodynorphin messenger RNA. However, the level of the preprodynorphin hybridization signal in bicuculline plus SKF-82958-treated rats was significantly lower than in saline plus SKF-82958-treated rats. In contrast, bicuculline, eticlopride or SKF-82958 by themselves increased basal preproenkephalin messenger RNA. However, there was no significant interaction among bicuculline, eticlopride and SKF-82958 on preproenkephalin messenger RNA levels. These data indicate that blockade of striatal GABA A receptors has only a subtle effect on acute dopamine agonist-induced changes in gene expression. These results are discussed in the context of local intrastriatal interactions.