Journal Article

Orexin-A up-regulates dopamine D2 receptor and mRNA in the nucleus accumbens Shell

Genis-Mendoza, Alma, Magdaleno-Madrigal, Víctor Manuel, Morales-Mulia, Marcela, Nicolini, Humberto, Morales-Mulia, Sandra

2020

Overview

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.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: Animal Anatomy / Animal Biochemistry / Animals / Biomedical and Life Sciences / Dopamine / Dopamine D1 receptors / Dopamine D2 receptors / dopamine receptors / Dopaminergic Neurons - cytology / Dopaminergic Neurons - drug effects / Dopaminergic Neurons - metabolism / Drug abuse / Drug addiction / G protein-coupled receptors / Gene expression / Gene Expression Regulation / genes / Histology / hypothalamus / Hypothalamus (lateral) / Injections, Intraventricular / Life Sciences / Male / Mesolimbic system / molecular biology / Morphology / Motivation / Neurons / Neuropeptides / neuroplasticity / Nucleus accumbens / Nucleus Accumbens - cytology / Nucleus Accumbens - drug effects / Nucleus Accumbens - metabolism / Orexin receptors / Orexins / Orexins - metabolism / Orexins - pharmacology / Original Article / Protein Binding / protein content / Proteins / quantitative polymerase chain reaction / Rats / Rats, Wistar / Receptors, Dopamine D1 - genetics / Receptors, Dopamine D1 - metabolism / Receptors, Dopamine D2 - genetics / Receptors, Dopamine D2 - metabolism / Reinforcement / RNA, Messenger - genetics / RNA, Messenger - metabolism / Signal Transduction / Stereotaxic Techniques / Synaptic plasticity / Transcription / transcription (genetics) / Ventral tegmentum / Western blotting