Orexin-A up-regulates dopamine D2 receptor and mRNA in the nucleus accumbens Shell
Por:
Morales-Mulia, Sandra, Magdaleno-Madrigal, Victor Manuel, Nicolini, Humberto, Genis-Mendoza, Alma, Morales-Mulia, Marcela
Publicada:
1 dic 2020
Resumen:
Orexins-A (OrxA) and -B (OrxB) neuropeptides are synthesized by a group
of neurons located in the lateral hypothalamus and adjacent perifornical
area, which send their projections to the mesolimbic dopaminergic
(DAergic) system including ventral tegmental area and nucleus accumbens
(NAc), where orexin receptors are expressed. NAc plays a central role in
reward-seeking behavior and drug abuse. NAc-neurons express dopamine-1
(D1R) and dopamine-2 (D2R) receptors. Orexins bind to their two cognate
G-protein-coupled receptors, orexin-receptor type-1 (Orx(1)R) and type-2
(Orx(2)R). Orexin receptor signaling is involved in behaviors such as
motivation and addiction. Orexin-containing neurons modulate DAergic
activity that is key in synaptic plasticity induced by addictive drugs.
However, the effect of OrxA on expression and content of DAergic
receptors in NAc is unknown. The purpose of this study was to
investigate whether OrxA can alter gene expression and protein levels of
D1R/D2R in NAc. Gene expression was evaluated by real-time PCR analysis
and protein levels by western blot in rats. The results show that
intracerebroventricular (i.c.v.) injection of OrxA increases both gene
transcription and protein content of D2R but fails to modify D1R. This
effect was also confirmed with OrxA infusion in NAc/Shell. Our results
demonstrate for the first time that OrxA induces up-regulation of gene
and protein of D2R in NAc. These findings support the hypothesis that
OrxA modulates the DAergic transmission and this may serve to understand
how orexin signaling enhances DA responses at baseline conditions and in
response to psychostimulants.
Filiaciones:
Morales-Mulia, Sandra:
Univ Nacl Autonoma Mexico, Fac Ciencias, Dept Biol Celular, Mexico City, DF, Mexico
Magdaleno-Madrigal, Victor Manuel:
INPRFM, Neurofisiol Control & Regulac, Direcc Neurociencias, Mexico City, DF, Mexico
Nicolini, Humberto:
Natl Inst Genom Med, Lab Genom Psychiat Dis Neurodegenerat & Addict, Mexico City, DF, Mexico
Genis-Mendoza, Alma:
Natl Inst Genom Med, Lab Genom Psychiat Dis Neurodegenerat & Addict, Mexico City, DF, Mexico
Hosp Psiquiatr Infantil Dr Juan N Navarro, Psychiat Attent Serv, Mexico City, DF, Mexico
Morales-Mulia, Marcela:
INPRFM, Bases Moleculares Adicc, Subdirecc Invest Clin, Calzada Mexico Xochimilco 101, Mexico City 14370, DF, Mexico
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