Decreased GABA(A)-receptor clustering results in enhanced anxiety and a bias for threat cues

Patients with panic disorders show a deficit of GABA(A) receptors in the hi ppocampus, parahippocampus and orbitofrontal cortex. Synaptic clustering of GABA(A) receptors in mice heterozygous for the gamma 2 subunit was reduced , mainly in hippocampus and cerebral cortex. The gamma 2(+/-) mice showed e nhanced behavioral inhibition toward natural aversive stimuli and heightene d responsiveness in trace fear conditioning and ambiguous cue discriminatio n learning. Implicit and spatial memory as well as long-term potentiation i n hippocampus were unchanged. Thus gamma 2(+/-) mice represent a model of a nxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associati ons. This model implicates GABA(A)-receptor dysfunction in patients as a ca usal predisposition to anxiety disorders.