Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats

Li，Wenfu1; Ren，Zhiheng1; Tang，Ying2; Fu，Yixin1; Sun，Shizhu1; Ding，Ruxuan1; Hou，Jiawei1; Mai，Yunlin1; Zhan，Bo1; Zhu，Yingxin1; Zuo，Wanhong3; Ye，Jiang Hong3; Fu，Rao1

2022

10.1038/s41386-022-01482-3

NEUROPSYCHOPHARMACOLOGY   影响因子和分区

0893-133X

1740-634X

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determine whether N/OFQ signaling contributes to the changes in both behavior phenotypes and RMTg activity of alcohol withdrawn (Post-EtOH) rats, we trained adult male Long-Evans rats, randomly assigned into the ethanol and Naïve groups to consume either 20% ethanol or water-only under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.

SCI

英语

其他

National Natural Science Foundation of China[82071496] ; Young Teacher Foundation of Sun Yat-sen University[5900018841219] ; Natural Science Foundation of Guangdong Province[2021 A1515010463] ; Shenzhen Science and Technology Program[202205303001697] ; China Postdoctoral Science Foundation[2022M711491]

Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry

Neurosciences ; Pharmacology & Pharmacy ; Psychiatry

WOS:000878487800001

SPRINGERNATURE

NEUROSCIENCE & BEHAVIOR

2-s2.0-85141217552

Scopus

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,2022,48(6).

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,48(6).

Li，Wenfu,et al."Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats".NEUROPSYCHOPHARMACOLOGY 48.6(2022).