Blockade of mGluR1 and mGluR5 in the lateral habenula produces the opposite effects in the regulation of depressive-like behaviors in the hemiparkinsonian rats.

Abstract

Depression is one of the most common non-motor symptoms in Parkinson's disease (PD) and the hyperactivity of the lateral habenula (LHb) may contribute to depression. The present study was performed to investigate the effects and mechanisms of group I metabotropic glutamate receptors (mGluRs) in the LHb on PD-related depressive-like behaviors. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) were used to establish the PD rat model. The group I mGluRs agonist and antagonists for mGluR1 and mGluR5 were microinjected into the LHb to observe their effects on PD-related depressive-like behaviors, electrical activities of the LHb, release of monoamines in the medial prefrontal cortex (mPFC) in sham and the lesioned rats. Lesions of the SNc induced depressive-like behaviors and hyperactivity of LHb neurons. Activation of group I mGluRs by 3,5-DHPG induced or enhanced depressive-like behaviors, increased the firing rate of the LHb neurons, and decreased dopamine (DA) and serotonin (5-HT) levels in the mPFC in the two groups of rats. Blockade of mGluR1 by YM298198 also produced similar effects with 3,5-DHPG, however, blockade of mGluR5 by MTEP produced opposite effects. Western blotting data showed that lesions of the SNc in rats down-regulated the expression of mGluR1 and mGluR5 in the LHb. These results suggest that mGluR1 and mGluR5 in the LHb induce opposite effects on depressive-like behaviors, which may attribute to the changed firing rate of LHb neurons by the presynaptic and postsynaptic mechanisms, and the changes in the monoamine levels.