Role of α1-GABA Receptors in the Serotonergic Dorsal Raphe Nucleus in Models of Opioid Reward, Anxiety, and Depression

Overview

Journal J Psychopharmacol

Publisher Sage Publications

Specialty Pharmacology

Date 2024 Jan 31

PMID 38293836

Authors

Chen Li

Bryan D McElroy

Jared Phillips

Nicholas S McCloskey

Xiangdang Shi

Ellen M Unterwald

Lynn G Kirby

Affiliations

Soon will be listed here.

Abstract

Background: The serotonin (5-hydroxytryptamine (5-HT))-mediated system plays an important role in stress-related psychiatric disorders and substance abuse. Our previous studies showed that stress and drug exposure can modulate the dorsal raphe nucleus (DRN)-5-HT system via γ-aminobutyric acid (GABA) receptors. Moreover, GABA receptor-mediated inhibition of serotonergic DRN neurons is required for stress-induced reinstatement of opioid seeking.

Aim/methods: To further test the role of GABA receptors in the 5-HT system in stress and opioid-sensitive behaviors, our current study generated mice with conditional genetic deletions of the GABA α1 subunit to manipulate GABA receptors in either the DRN or the entire population of 5-HT neurons. The GABA α1 subunit is a constituent of the most abundant GABA subtype in the brain and the most highly expressed subunit in 5-HT DRN neurons.

Results: Our results showed that mice with DRN-specific knockout of α1-GABA receptors exhibited a normal phenotype in tests of anxiety- and depression-like behaviors as well as swim stress-induced reinstatement of morphine-conditioned place preference. By contrast, mice with 5-HT neuron-specific knockout of α1-GABA receptors exhibited an anxiolytic phenotype at baseline and increased sensitivity to post-morphine withdrawal-induced anxiety.

Conclusions: Our data suggest that GABA receptors on 5-HT neurons contribute to anxiety-like behaviors and sensitivity of those behaviors to opioid withdrawal.

Citing Articles

Role of the Dorsal Raphe Nucleus in Pain Processing.

Zhang H, Li L, Zhang X, Ru G, Zang W Brain Sci. 2024; 14(10).

PMID: 39451996 PMC: 11506261. DOI: 10.3390/brainsci14100982.

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