|  Help  |  About  |  Contact Us

Publication : Ethanol consumption and sedation are altered in mice lacking the glycine receptor α2 subunit.

First Author  San Martin L Year  2020
Journal  Br J Pharmacol Volume  177
Issue  17 Pages  3941-3956
PubMed ID  32436225 Mgi Jnum  J:308517
Mgi Id  MGI:6729765 Doi  10.1111/bph.15136
Citation  San Martin L, et al. (2020) Ethanol consumption and sedation are altered in mice lacking the glycine receptor alpha2 subunit. Br J Pharmacol 177(17):3941-3956
abstractText  BACKGROUND AND PURPOSE: The precise mechanism/s of action of ethanol, although studied for many years, are not well understood. Like other drugs of abuse, ethanol affects dopamine levels in the nucleus accumbens (nAc), an important region of the mesolimbic system, causing a reinforcing effect. It has been shown that glycine receptors (GlyRs) present in the nAc are potentiated by clinically relevant concentrations of ethanol, where alpha1 and alpha2 are the predominant subunits expressed. EXPERIMENTAL APPROACH: Using a combination of electrophysiology and behavioural assays, we studied the involvement of GlyR alpha2 subunits on the effects of low and high doses of ethanol, as well as on consumption using mice lacking the GlyR alpha2 subunit (male Glra2(-/Y) and female Glra2(-/-) ). KEY RESULTS: GlyR alpha2 subunits exist in accumbal neurons, since the glycine-evoked currents and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in Glra2(-/Y) mice were drastically decreased. In behavioural studies, differences in ethanol consumption and sedation were observed between wild-type (WT) and Glra2 knockout (KO) mice. Using the drinking in the dark (DID) paradigm, we found that Glra2(-/Y) mice presented a binge-like drinking behaviour immediately when exposed to ethanol rather than the gradual consumption seen in WT animals. Interestingly, the effect of knocking out Glra2 in female (Glra2(-/-) ) mice was less evident, since WT female mice already showed higher DID. CONCLUSION AND IMPLICATIONS: The differences in ethanol consumption between WT and KO mice provide additional evidence supporting the conclusion that GlyRs are biologically relevant targets for the sedative and rewarding properties of ethanol.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

3 Bio Entities

0 Expression