Putative role of monoamines in the antidepressant-like mechanism induced by striatal MT2 blockade

•Antidepressant effects triggered by MT2 blockade in the striatum.•Association of striatal MT2 blockade and REMSD generates decreases 5-HT.•4-P-PDOT increased 5-HT and DA turnovers. It has been observed that the secretion pattern of melatonin is modified in Parkinson's disease (PD). Hence, it i...

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Bibliographic Details
Published in:Behavioural brain research 2014-12, Vol.275, p.136-145
Main Authors: Noseda, Ana Carolina D., Rodrigues, Lais S., Targa, Adriano D.S., Aurich, Mariana F., Vital, Maria A.B.F., Da Cunha, Cláudio, Lima, Marcelo M.S.
Format: Article
Language:English
Subjects:
4-P-PDOT
8-M-PDOT
Animals
Biogenic Monoamines - metabolism
Biological and medical sciences
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Corpus Striatum - physiology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Depression - drug therapy
Depression - etiology
Depression - metabolism
Disease Models, Animal
Dopamine
Insecticides - toxicity
Male
Medical sciences
Neurology
Neuropharmacology
Parkinson's disease
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Rats, Wistar
Receptors, Melatonin - antagonists & inhibitors
Rotenone
Rotenone - toxicity
Serotonin
Sleep Deprivation
Statistics as Topic
Swimming - psychology
Tetrahydronaphthalenes - pharmacology
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Summary:•Antidepressant effects triggered by MT2 blockade in the striatum.•Association of striatal MT2 blockade and REMSD generates decreases 5-HT.•4-P-PDOT increased 5-HT and DA turnovers. 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.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2014.09.007