TY  - JOUR
N2  - 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.
EP  - 1270
A1  - Wei, Shoupeng
A1  - Zheng, Lei
A1  - Chang, Jinlong
A1  - Jiang, Jian
A1  - Zhou, Zhiyu
A1  - Liao, Huanquan
A1  - Song, Kun
A1  - Liu, Xiaoma
A1  - Chi, Xinjin
A1  - Li, Huiliang
A1  - Kuang, Xin
A1  - Li, Ningning
VL  - 47
UR  - http://doi.org/10.1111/acer.15094
ID  - discovery10169637
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
PB  - Wiley
Y1  - 2023/07//
TI  - G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice
AV  - public
JF  - Alcohol: Clinical and Experimental Research
IS  - 7
KW  - G protein-coupled receptor 158
KW  -  ethanol
KW  -  loss of righting reflex
KW  -  sensitivity
SP  - 1261
SN  - 0145-6008
ER  -