Altered response to benzodiazepine anxiolytics in mice lacking GABA B(1) receptors.
Recently, we demonstrated that mice lacking the GABA(B(1)) subunit were more anxious than wild-type animals in several behavioural paradigms, most notably in the light-dark test. In an attempt to assess the effects of classical benzodiazepine anxiolytics on anxiety-like behaviour observed in these mice, animals were administered either chlordiazepoxide (10 mg/kg, p.o.) or diazepam (7.5 mg/kg, p.o.) prior to testing in the light-dark box. Surprisingly, in contrast with the wild-type mice, neither benzodiazepines decreased anxiety-like behaviour in GABA(B(1))(-/-) mice. These data suggest that targeted deletion of GABA(B(1)) subunit alters GABA(A) receptor function in vivo.
Neuroscience Research, Novartis Institutes for BioMedical Research WSJ 386.344, Novartis Pharma AG., Basel CH-4002, Switzerland.
Cedric
C
Mombereau
Klemens
K
Kaupmann
Herman
H
van der Putten
John F
JF
Cryan
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D002707:Chlordiazepoxide / Q000494:pharmacology* / Q000627:therapeutic use; D003975:Diazepam / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000235:genetics / Q000502:physiology*
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D002707:Chlordiazepoxide; D003975:Diazepam