Behavioral evaluation of mice deficient in GABAB(1) receptor isoforms in tests of unconditioned anxiety

Rationale Emerging data support a role for GABA(B) receptors in anxiety. GABA(B) receptors are comprised of a heterodimeric complex of GABA(B1) and GABA(B2) receptor subunits. The predominant neuronal GABA(B1) receptor isoforms are GABA(B(1a)) and GABA(B(1b)). Recent findings indicate specific roles for these isoforms in conditioned fear responses, although their influence on behavior in tests of unconditioned anxiety is unknown. Objective The aim of this study was to examine the role of the GABA(B(1)) isoforms in unconditioned anxiety. Materials and methods Mice deficient in the GABA(B(1a)) or GABA(B(1b)) receptor isoforms were examined in a battery of anxiety tests. Results In most tests, genotype did not significantly affect anxious behavior, including the elevated plus maze, marble burying, and stress-induced hypothermia tests. Corticosterone and adrenocorticotropic hormone levels were similarly unaffected by genotype. Female, but not male, GABAB((1a))(-/-) and GABA(B(1b)) mice showed increased anxiety relative to wild-type controls in the elevated zero maze. In the staircase test, male GABA(B(1b))(-/-) mice defecated more than male GABA(B(1a))(-/-) mice, although no other test parameter was influenced by genotype. In the light-dark box, female GABA(B(1a))(-/-) mice spent less time in the light compartment compared to the GABA(B(1b))(-/-) females, whereas male GABA(B(1b))(-/-) mice made fewer light-dark transitions than GABA(B(1a))(-/-) males. Conclusions Specific roles for either GABA(B(1)) isoform in unconditioned anxiety were not explicit. This differs from their contribution in conditioned anxiety and from the anxious phenotype of GABA(B1) and GABA(B2) subunit knockout mice. The findings suggest that the GABA(B(1)) isoforms have specific relevance for anxiety with a cognitive component, rather than for innate anxiety per se.