Activation but not blockade of GABAB receptors during early-life alters anxiety in adulthood in BALB/c mice.
Although the underlying pathophysiology of anxiety disorders is unknown it is clear that a combination of genetic and environmental factors in early life predispose to disease risk. Preclinical research increasingly suggests an important role for the GABAB receptor in modulating anxiety behaviour, with GABAB receptor deficient mice having increased anxiety behaviour. Previous studies have highlighted critical windows during development where adult anxiety behaviour is primed. However, little is known regarding the role played by the GABAB receptors in the developmental processes that underlie adult anxiety behaviour. To this end, we treated male BALB/c mouse pups with the either the selective GABAB receptor agonist, R-baclofen (2 mg/kg, s.c), the GABAB receptor antagonist CGP 52432 (10 mg/kg and 30 mg/kg) or vehicle from postnatal days (P) 14-28. The anxiety behaviour of these mice was then assessed in adulthood (P62 onwards) in a battery of behavioural tests comprising; the stress induced hyperthermia (SIH) test, defensive marble burying (DMB), elevated-plus maze (EPM) and the forced swim test (FST). Postnatal R-baclofen treatment resulted in increased anxiety-like behaviour in the EPM as shown by approach-avoidance and ethological measures. Other behavioural measures were not significantly altered. Interestingly, blockade of GABAB receptors with CGP52432 in early life caused no alterations in emotional behaviour. These data suggest that during early life GABAB receptor signalling can play a functional role in programing anxiety behaviour in adulthood. The underlying neurodevelopmental processes underlying these effects remain to be discovered.
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland.
Fabian F
FF
Sweeney
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Olivia F
OF
O'Leary
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: j.cryan@ucc.ie.
John F
JF
Cryan
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D001418:Baclofen / Q000633:toxicity; D001596:Benzylamines / Q000494:pharmacology; D003674:Defense Mechanisms; D004195:Disease Models, Animal; D005334:Fever / Q000150:complications / Q000209:etiology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010721:Phosphinic Acids / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications; D013550:Swimming / Q000523:psychology
D001596:Benzylamines; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C083008:CGP 52432; D001418:Baclofen
Anxiety; Baclofen; CGP52432; Development; Early-life; GABA(B)