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, GABA_B(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.