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Altered anxiety and depression-related behaviour in mice lacking GABAB(2) receptor subunits

Mombereau, Cedric1; Kaupmann, Klemens1; Gassmann, Martin2; Bettler, Bernhard2; van der Putten, Herman1; Cryan, John F.1 CA

MOTIVATION, EMOTION, FEEDING, DRINKING
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Metabotropic GABAB receptors predominantly function as heterodimers of GABAB(1) and GABAB(2) subunits, but GABAB(1) can also form functional receptors in the absence of GABAB(2). Mice lacking the GABAB(1) subunit have altered behavioural responses in tests for anxiety and depression. In these studies, we investigated anxiety and depression in GABAB(2)-deficient mice. We compared the effects directly with that of genetic deletion of the GABAB(1) receptor subunit. Both GABAB(1) and GABAB(2)-deficient mice were found to be more anxious than wild type in the light–dark box paradigm. In contrast, these mice exhibited an antidepressant-like behaviour in the forced swim test. Taken together, these data suggest that heterodimeric GABAB(1,2) receptors are required for the normal regulation of emotional behaviour.

1Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

2Pharmazentrum, Department of Clinical-Biological Sciences, Klingelbergstr. 50-70, CH-4056 Basel, Switzerland

CACorresponding author: john_f.cryan@pharma.novartis.com

Received 2 December 2004; accepted 10 January 2005

© 2005 Lippincott Williams & Wilkins, Inc.