Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation

摘要: In cortex and hippocampus, protracted (>4 weeks) social isolation of adult male mice alters the subunit expression GABA type A receptors (GABAA-Rs) as follows: (i) mRNAs encoding GABAA-R α1, α2, γ2 subunits are decreased by ≈50%, whereas those α4 α5 increased ≈100%; (ii) similarly, synaptic membrane α1 protein is down-regulated, that up-regulated; (iii) binding [3H]flumazenil to hippocampal membranes decreased. Behaviorally, socially isolated (SI) resistant sedative effects positive allosteric modulators diazepam (DZP) zolpidem. This resistance seems be attributable decrease α1-containing GABAA-Rs. Paradoxically, DZP, which, unlike zolpidem, acts at α5-containing GABAA-Rs, increases locomotor activity SI mice. Imidazenil, which fails modulate α1-, α4-, α6-containing GABAA-Rs but a selective modulator also in Importantly, responded muscimol, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one, allopregnanolone similar group-housed These data suggest switch (a α1/α2 an increase subunits) composition heteropentameric assembly without change total number occurs during isolation. Thus, repertoire DZP imidazenil actions appears elicited modulation overexpressing subunits. Benzodiazepine response mediated expected silent or reduced.