Role of α1-GABAA receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression
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)A receptors. Moreover, GABAA receptor-mediated inhibition of serotonergic DRN neurons is required for stress-induced reinstatement of opioid seeking.
AIM/METHODS: To further test the role of GABAA receptors in the 5-HT system in stress and opioid-sensitive behaviors, our current study generated mice with conditional genetic deletions of the GABAA α1 subunit to manipulate GABAA receptors in either the DRN or the entire population of 5-HT neurons. The GABAA α1 subunit is a constituent of the most abundant GABAA 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-GABAA 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-GABAA receptors exhibited an anxiolytic phenotype at baseline and increased sensitivity to post-morphine withdrawal-induced anxiety.
CONCLUSIONS: Our data suggest that GABAA receptors on 5-HT neurons contribute to anxiety-like behaviors and sensitivity of those behaviors to opioid withdrawal.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of psychopharmacology (Oxford, England) - 38(2024), 2 vom: 31. Feb., Seite 188-199 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Chen [VerfasserIn] |
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| Links: |
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| Themen: |
α1-GABAA |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 09.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/02698811241227672 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Role of α1-GABAA receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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)A receptors. Moreover, GABAA receptor-mediated inhibition of serotonergic DRN neurons is required for stress-induced reinstatement of opioid seeking | ||
| 520 | |a AIM/METHODS: To further test the role of GABAA receptors in the 5-HT system in stress and opioid-sensitive behaviors, our current study generated mice with conditional genetic deletions of the GABAA α1 subunit to manipulate GABAA receptors in either the DRN or the entire population of 5-HT neurons. The GABAA α1 subunit is a constituent of the most abundant GABAA subtype in the brain and the most highly expressed subunit in 5-HT DRN neurons | ||
| 520 | |a RESULTS: Our results showed that mice with DRN-specific knockout of α1-GABAA 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-GABAA receptors exhibited an anxiolytic phenotype at baseline and increased sensitivity to post-morphine withdrawal-induced anxiety | ||
| 520 | |a CONCLUSIONS: Our data suggest that GABAA receptors on 5-HT neurons contribute to anxiety-like behaviors and sensitivity of those behaviors to opioid withdrawal | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a McCloskey, Nicholas S |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiangdang |e verfasserin |4 aut | |
| 700 | 1 | |a Unterwald, Ellen M |e verfasserin |4 aut | |
| 700 | 1 | |a Kirby, Lynn G |e verfasserin |4 aut | |
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