Wei, Shoupeng;
Zheng, Lei;
Chang, Jinlong;
Jiang, Jian;
Zhou, Zhiyu;
Liao, Huanquan;
Song, Kun;
... Li, Ningning; + view all
(2023)
G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice.
Alcohol: Clinical and Experimental Research
, 47
(7)
pp. 1261-1270.
10.1111/acer.15094.
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G protein coupled receptor 158 modulates sensitivity to the sedative hypnotic effect.pdf - Accepted Version Download (1MB) | Preview |
Abstract
BACKGROUND: Sensitivity to ethanol is used to assess a predisposition to recover from unconsciousness induced by excessive ethanol. The role of G protein-coupled receptor 158 (GPR158) in modulating sensitivity to the sedative-hypnotic effect of ethanol has not been investigated. METHODS: Loss of righting reflex (LORR) is a behavioral feature to indicate a state of hypnosis in rodents. In this study, Gpr158-/- mice and wild-type (WT) littermates (n = 8/genotype) were tested with the paradigms of LORR induced by a dose of 3.5 g/kg ethanol, open-field test (OFT) and blood ethanol concentration measurement. The OFT was used to examine the role of GPR158 in the ethanol effect on motor activity in Gpr158-/- mice (n = 6/genotype). Furthermore, CamK2A-Cre;Gpr158fl/fl (n = 9) and Vgat-Cre;Gpr158fl/fl mice (n = 10) went through LORR test and OFT compared to the controls (n= 9 and 8, respectively). RESULTS: Gpr158 deficiency led to a prolonged LORR duration by 110.6% (t14 = -5.241, p = 0.0001), without altering spontaneous activity (t14 = -0.718, p = 0.485) or ethanol metabolism (F1, 8 = 0.259, p = 0.625). Gpr158 knockout did not affect the ethanol effect on locomotion (F1, 10 = 0.262, p = 0.62). Furthermore, LORR duration became longer in the conditional knockouts of Gpr158 within calcium/calmodulin dependent protein kinase II alpha-positive (CamK2A+ ) neurons by 69% (t16 = -2.914, p = 0.01) and vesicular GABA transporter-positive (Vgat+ ) neurons by 92% (t9.802 = -2.519, p = 0.023), respectively, while locomotion was not altered in Camk2A-Cre;Gpr158fl/fl (t16 = 0.49, p = 0.631) or Vgat-Cre;Gpr158fl/fl mice (t16 = 0.035, p = 0.972). CONCLUSIONS: This study reveals a critical role of neuronal GPR158 in shaping sensitivity to the sedative-hypnotic effect of ethanol, suggesting that GPR158 may be a potential target for treating alcohol use disorder.
| Type: | Article |
|---|---|
| Title: | G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/acer.15094 |
| Publisher version: | http://doi.org/10.1111/acer.15094 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | G protein-coupled receptor 158, ethanol, loss of righting reflex, sensitivity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10169637 |
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