Unilateral lesion of the nigrostriatal pathway decreases the response of GABA interneurons in the dorsal raphe nucleus to 5-HT1A receptor stimulation in the rat

Abstract

This study examined the firing rate and pattern of electrophysiologically and chemically identified GABA interneurons in the dorsal raphe nucleus (DRN), and role of 5-HT1A receptor agonist 8-OH-DPAT and the medial prefrontal cortex (mPFC) in the firing activity in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The interneurons in rats with lesions of the SNc showed a more burst-firing, while having no change in the firing rate; the mPFC and combined mPFC and SNc lesions in rats decreased the firing rate of the interneurons and firing pattern shifted towards a more burst-firing compared to rats with sham lesions of the SNc, respectively. In rats with sham lesions of the SNc, administration of 8-OH-DPAT (1–243μg/kg, i.v.) produced excitatory–inhibitory, excitatory and inhibitory effects in the firing rate of individual interneurons. However, when these effects were averaged over the group, 8-OH-DPAT had no significant effect on firing rate. In rats with lesions of the SNc, mPFC and the paired lesions, 8-OH-DPAT, at the same doses, inhibited all interneurons tested, respectively. Cumulative doses producing inhibition in rats with the paired lesions were higher than that of rats with lesions of the mPFC. In contrast to rats with sham lesions of the SNc, SNc lesion reduced expression of 5-HT1A receptor on parvalbumin positive neurons in the DRN, a subpopulation of GABA interneurons. Our results indicate that the SNc and mPFC regulate the firing activity of GABA interneurons in the DRN. Furthermore, response of likely GABA interneurons to systemic administration of 8-OH-DPAT is altered by lesion of the SNc and mPFC.