Dopaminergic D2 receptor is a key player in the substantia nigra pars compacta neuronal activation mediated by REM sleep deprivation

Abstract

Currently, several studies addresses the novel link between sleep and dopaminergic neurotransmission, focusing most closely on the mechanisms by which Parkinson's disease (PD) and sleep may be intertwined. Therefore, variations in the activity of afferents during the sleep cycles, either at the level of DA cell bodies in the ventral tegmental area (VTA) and/or substantia nigra pars compacta (SNpc) or at the level of dopamine (DA) terminals in limbic areas may impact functions such as memory. Accordingly, we performed striatal and hippocampal neurochemical quantifications of DA, serotonin (5-HT) and metabolites of rats intraperitoneally treated with haloperidol (1.5 mg/kg) or piribedil (8 mg/kg) and submitted to REM sleep deprivation (REMSD) and sleep rebound (REB). Also, we evaluated the effects of REMSD on motor and cognitive parameters and SNpc c-Fos neuronal immunoreactivity. The results indicated that DA release was strongly enhanced by piribedil in the REMSD group. In opposite, haloperidol prevented that alteration. A c-Fos activation characteristic of REMSD was affected in a synergic manner by piribedil, indicating a strong positive correlation between striatal DA levels and nigral c-Fos activation. Hence, we suggest that memory process is severely impacted by both D2 blockade and REMSD and was even more by its combination. Conversely, the activation of D2 receptor counteracted such memory impairment. Therefore, the present evidence reinforce that the D2 receptor is a key player in the SNpc neuronal activation mediated by REMSD, as a consequence these changes may have direct impact for cognitive and sleep abnormalities found in patients with PD. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 3,4-dihydroxyphenylacetic acid; 5-HIAA; 5-HT; 5-hydroxyindoleacetic acid; DA; DAT-KO; DHPG; DI; DOPAC; Dopamine; HVA; Haloperidol; LDT; MPTP; NA; PD; PPT; Parkinson's disease; Parkinson’s disease; Piribedil; REB; REM; REM sleep deprivation; REMSD; SNpc; Substantia nigra pars compacta; VTA; dihydroxyphenylglycol; discrimination index; dopamine; dopamine transporter knockout; homovanillic acid; laterodorsal tegmental nuclei; noradrenaline; pedunculopontine tegmental nucleus; rapid eye movement; rebound; serotonin; substantia nigra pars compacta; ventral tegmental area.