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- Title
Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats.
- Authors
Wenfu Li; Bo Zhan; Yingxin Zhu; Zhiheng Ren; Ruxuan Ding; Yixin Fu; Jiawei Hou; Yunlin Mai; Ying Tang; Wanhong Zuo; Jianghong Ye; Rao Fu
- Abstract
Objective: Repeated alcohol drinking and withdrawal induce negative affective states, promoting alcohol use disorders (AUDs) development, linked with mesolimbic dopamine (DA) hypofunction but lack clear mechanisms. The present study explores the role of nociceptin (N/OFQ) signaling of GABAergic VTA-projecting neurons in the rostromedial tegmental nucleus (RMTg) on the adverse behaviors associated with AUDs. Methods: Adult Long-Evans rats were trained to chronically intermittently consume water (Naive) or alcohol (Post-EtOH). The approaches, including FISH and immunostaining combined with retrograde tracing, LCM coupled with qPCR, chemogenetic and pharmacological tools combined with behavioral tests, and electrophysiological recording, were used in this study. Results: The RMTg neurons express Pnoc and Oprl1 genes and exert an inhibitory input onto VTA DA neurons. Chemogenetic inactivating RMTg decreased the cFos expression, mitigated anxiety and depressive symptoms, and reduced alcohol consumption in Post-EtOH rats, which was mimicked by local activating nociceptin receptors (NOP). Moreover, blocking RMTg NOP increased cFos expression and elicited the above aberrant behaviors in naïve rats. Additionally, chemogenetic inactivating RMTg neurons reduced GABA release and accelerated VTA DA neurons' spontaneous firings. Finally, pharmacological inhibiting unilateral RMTg combined with activating DA D1/2 receptors in the contralateral (but not ipsilateral) NAc mitigated the negative moods in Post- EtOH rats. Conclusion: RMTg N/OFQ signaling plays a crucial role in the aversive behaviors during AUDs. Intervention targeting RMTg NOP may help those suffering from AUDs. These results help us understand the molecular and neural circuits mechanisms of DA hypofunction linked with negative emotion associated with AUDs.
- Subjects
NOCICEPTIN; ALCOHOLISM; DOPAMINE; LABORATORY rats; GABAERGIC neurons; ALCOHOL drinking; ALCOHOL
- Publication
Anatomy: International Journal of Experimental & Clinical Anatomy, 2022, Vol 16, pS76
- ISSN
1307-8798
- Publication type
Abstract