title: 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'.
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Setor de Ciências Biológicas, Av. Francisco H. dos Santos s/n, 81.531-990, Caixa Postal 19031, Curitiba, PR, Brazil.
authors.forename: Mariana B
authors.initials: MB
authors.lastname: Proença
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Dombrowski
authors.forename: Claudio
authors.initials: C
authors.lastname: Da Cunha
authors.forename: Luana
authors.initials: L
authors.lastname: Fischer
authors.forename: Anete C
authors.initials: AC
authors.lastname: Ferraz
authors.forename: Marcelo M S
authors.initials: MM
authors.lastname: Lima
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D059907:Functional Neuroimaging; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010891:Piribedil / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012701:Serotonin; D012892:Sleep Deprivation / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012701:Serotonin; D010891:Piribedil; D006220:Haloperidol; D004298:Dopamine
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