Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats
Recent studies indicate that stimulation of the rostromedial tegmental nucleus (RMTg) can drive a negative affective state and that nociceptin/orphanin FQ (N/OFQ) may play a role in affective disorders and drug addiction. The N/OFQ precursor prepronociceptin encoding genes Pnoc are situated in RMTg neurons. To determine whether N/OFQ signaling contributes to the changes in both behavior phenotypes and RMTg activity of alcohol withdrawn (Post-EtOH) rats, we trained adult male Long-Evans rats, randomly assigned into the ethanol and Naïve groups to consume either 20% ethanol or water-only under an intermittent-access procedure. Using the fluorescence in situ hybridization technique combined with retrograde tracing, we show that the ventral tegmental area projecting RMTg neurons express Pnoc and nociceptin opioid peptide (NOP) receptors encoding gene Oprl1. Also, using the laser capture microdissection technique combined with RT-qPCR, we detected a substantial decrease in Pnoc but an increase in Oprl1 mRNA levels in the RMTg of Post-EtOH rats. Moreover, RMTg cFos expression is increased in Post-EtOH rats, which display anxiety- and depression-like behaviors. Intra-RMTg infusion of the endogenous NOP agonist nociceptin attenuates the aversive behaviors in Post-EtOH rats without causing any notable change in Naïve rats. Conversely, intra-RMTg infusion of the NOP selective antagonist [Nphe]nociceptin(1-13)NH elicits anxiety- and depression-like behaviors in Naïve but not Post-EtOH rats. Furthermore, intra-RMTg infusion of nociceptin significantly reduces alcohol consumption. Thus, our results show that the deficiency of RMTg NOP signaling during alcohol withdrawal mediates anxiety- and depression-like behaviors. The intervention of NOP may help those individuals suffering from alcohol use disorders.
|WOS Accession No|
|ESI Research Field|
NEUROSCIENCE & BEHAVIOR
Cited Times [WOS]:0
|Document Type||Journal Article|
|Department||Department of Biology|
1.Department of Anatomy,School of Medicine,Shenzhen Campus of Sun Yat-sen University,Sun Yat-sen University,Shenzhen,Guangdong,518107,China
2.Department of Biology,School of Life Science,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
3.Department of Anesthesiology,Pharmacology,Physiology & Neuroscience,Rutgers,The State University of New Jersey,New Jersey Medical School,Newark,07103,United States
Li，Wenfu,Ren，Zhiheng,Tang，Ying,et al. Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats[J]. NEUROPSYCHOPHARMACOLOGY,2022.
Li，Wenfu.,Ren，Zhiheng.,Tang，Ying.,Fu，Yixin.,Sun，Shizhu.,...&Fu，Rao.(2022).Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats.NEUROPSYCHOPHARMACOLOGY.
Li，Wenfu,et al."Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats".NEUROPSYCHOPHARMACOLOGY (2022).
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