Peer-Reviewed Journal Details
Mandatory Fields
Sweeney, FE;O'Leary, OF;Cryan, JF
2014
June
Neuropharmacology
Activation but not blockade of GABA(B) receptors during early-life alters anxiety in adulthood in BALB/c mice
Validated
WOS: 10 ()
Optional Fields
DEPRESSION-RELATED BEHAVIOR ALLOSTERIC MODULATION LACKING GABA(B(1)) AGONIST BACLOFEN ANIMAL-MODELS MOUSE STRAINS STRESS LIGANDS TESTS RESPONSES
81
303
310
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 GABA(B) receptor in modulating anxiety behaviour, with GABA(B) 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 GABA(B) 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 GABA(B) receptor agonist, R-baclofen (2 mg/kg, s.c), the GABA(B) 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 GABB receptors with CGP52432 in early life caused no alterations in emotional behaviour. These data suggest that during early life GABA(B) receptor signalling can play a functional role in programing anxiety behaviour in adulthood. The underlying neurodevelopmental processes underlying these effects remain to be discovered. (C) 2013 Elsevier Ltd. All rights reserved.
OXFORD
0028-3908
10.1016/j.neuropharm.2013.08.039
Grant Details