MT2 melatonin receptors expressed in the olfactory bulb modulate depressive-like behavior and olfaction in the 6-OHDA model of Parkinson's disease.

Melatonin MT1 and MT2 receptors are expressed in the glomerular layer of the olfactory bulb (OB); however, the role of these receptors has not been evaluated until now. Considering the association of the OB with olfactory and depressive disorders in Parkinson's disease (PD), we sought to investigate the involvement of melatonin receptors in these non-motor disturbances in an intranigral 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. We demonstrate the presence of functional melatonin receptors in dopaminergic neurons of the glomerular layer. Local administration of melatonin (MLT, 1 μg/μl), luzindole (LUZ, 5 μg/μl) or the MT2-selective receptor drug 4-P-PDOT (5 μg/μl) reversed the depressive-like behavior elicited by 6-OHDA. Sequential administration of 4-P-PDOT and MLT (5 μg/μl, 1 μg/μl) promoted additive antidepressant-like effects. In the evaluation of olfactory discrimination, LUZ induced an olfactory impairment when associated with the nigral lesion-induced impairment. Thus, our results suggest that melatonin MT2 receptors expressed in the glomerular layer are involved in depressive-like behaviors and in olfactory function associated with PD.