title: Putative role of monoamines in the antidepressant-like mechanism induced by striatal MT2 blockade.
abstract: It has been observed that the secretion pattern of melatonin is modified in Parkinson's disease (PD). Hence, it is hypothesized that dysregulations of melatonin MT2 receptors may be involved in the installation of depression in PD patients. Together with recent evidence based on the use of the intranigral rotenone model of PD, have led to the hypothesis that modulating the striatal MT2 receptor could provide a more comprehensive understanding of the antidepressant properties triggered. To further investigate this issue, male Wistar rats were infused with intranigral rotenone (12μg/μL) and seven days later subjected to a rapid eye movement sleep deprivation (REMSD) for 24h. After, we injected within the striatum the MT2 selective agonist, 8-M-PDOT (10μg/μL), the MT2 selective antagonist, 4-P-PDOT (5μg/μL) or vehicle. Subsequently, they were tested in the forced swimming test and were allowed to perform the sleep rebound (REB). Then, the rats were re-tested, and the striatum, hippocampus and substantia nigra pars compacta (SNpc) were collected for neurochemical purposes. Results indicated substantial antidepressant effects promoted by the blockade of striatal MT2 receptors that were potentiated by REMSD. MT2 activation increased DA levels in the striatum and hippocampus, while MT2 blockade increase DA in the SNpc. 4-P-PDOT treatment of the rotenone REMSD group generated a decrement in 5-HT levels within the striatum, hippocampus and SNpc. However, increased 5-HT turnover was observed among these structures. Therefore, we demonstrated the neurochemical antidepressant effect induced by striatal MT2 blockage associated with REMSD in the rotenone model of PD.
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Ana Carolina D
authors.initials: AC
authors.lastname: Noseda
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Lais S
authors.initials: LS
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Adriano D S
authors.initials: AD
authors.lastname: Targa
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Mariana F
authors.initials: MF
authors.lastname: Aurich
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Maria A B F
authors.initials: MA
authors.lastname: Vital
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Da Cunha
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: marcelomslima.neuro@gmail.com.
authors.forename: Marcelo M S
authors.initials: MM
authors.lastname: Lima
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D007306:Insecticides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors; D012402:Rotenone / Q000633:toxicity; D012892:Sleep Deprivation; D013223:Statistics as Topic; D013550:Swimming / Q000523:psychology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: C114459:4-phenyl-2-propionamidotetraline; C533877:8-methoxy-2-propionamidotetralin; D015306:Biogenic Monoamines; D007306:Insecticides; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; D012402:Rotenone
keywords: 4-P-PDOT; 8-M-PDOT; Dopamine; Parkinson's disease; Rotenone; Serotonin