| First Author | Li C | Year | 2024 |
| Journal | J Psychopharmacol | Volume | 38 |
| Issue | 2 | Pages | 188-199 |
| PubMed ID | 38293836 | Mgi Jnum | J:360592 |
| Mgi Id | MGI:7834564 | Doi | 10.1177/02698811241227672 |
| Citation | Li C, et al. (2024) Role of alpha1-GABA(A) receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression. J Psychopharmacol 38(2):188-199 |
| abstractText | 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 gamma-aminobutyric acid (GABA)(A) receptors. Moreover, GABA(A) 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(A) receptors in the 5-HT system in stress and opioid-sensitive behaviors, our current study generated mice with conditional genetic deletions of the GABA(A) alpha1 subunit to manipulate GABA(A) receptors in either the DRN or the entire population of 5-HT neurons. The GABA(A) alpha1 subunit is a constituent of the most abundant GABA(A) 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 alpha1-GABA(A) 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 alpha1-GABA(A) receptors exhibited an anxiolytic phenotype at baseline and increased sensitivity to post-morphine withdrawal-induced anxiety. CONCLUSIONS: Our data suggest that GABA(A) receptors on 5-HT neurons contribute to anxiety-like behaviors and sensitivity of those behaviors to opioid withdrawal. |
