Cerebellar GABA(A) receptors and anxiolytic action of diazepam.
Alcohol-sensitive ANT rats have a point mutation in the cerebellum-enriched GABA(A) receptor alpha6 subunit, which makes this subunit and the ANT rats in vivo highly sensitive to benzodiazepine agonists. In the elevated plus maze test of anxiety, diazepam produced a greater anxiolytic response in the ANT rats than in the control, alcohol-insensitive AT rats. The ANT rats were less sensitive to the sedative effect of diazepam in the staircase test of exploration. The results thus suggest that the mutant cerebellar granule cell layer receptors can participate in GABA(A) receptor-activation-induced anxiolysis.
Vekovischeva
O Y
OY
Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520, Turku, Finland.
Haapalinna
A
A
Sarviharju
M
M
Honkanen
A
A
Korpi
E R
ER
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D002531:Cerebellum / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology*; D000431:Ethanol; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D017354:Point Mutation; D051381:Rats; D011922:Rats, Mutant Strains; D011930:Reaction Time; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*
D011963:Receptors, GABA-A; D000431:Ethanol; D003975:Diazepam