Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues


Patients with panic disorders show a deficit of GABAA receptors in the hippocampus, parahippocampus and orbitofrontal cortex. Synaptic clustering of GABAA receptors in mice heterozygous for the γ2 subunit was reduced, mainly in hippocampus and cerebral cortex. The γ2+/– mice showed enhanced behavioral inhibition toward natural aversive stimuli and heightened responsiveness in trace fear conditioning and ambiguous cue discrimination learning. Implicit and spatial memory as well as long-term potentiation in hippocampus were unchanged. Thus γ2+/– mice represent a model of anxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associations. This model implicates GABAA-receptor dysfunction in patients as a causal predisposition to anxiety disorders.

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Figure 1: Region-specific decrease of [3H]flumazenil binding and loss of GABAA-receptor clusters in γ2+/– mice.
Figure 2: Single-channel properties of GABAA receptors and long-term potentiation in γ2+/– mice.
Figure 3: Behavioral responses to natural aversive stimuli.
Figure 4: Reversal of behavioral responses to natural aversive stimuli by diazepam.
Figure 5: Behavioral responses to learned aversive stimuli.


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We thank René Misslin for advice in the preliminary experiments and Guadalupe Reyes for technical assistance. This work was supported by the Swiss National Science Foundation (grant Nr: 31-39702.93 to B.L.)

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Correspondence to Hanns Mohler.

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Crestani, F., Lorez, M., Baer, K. et al. Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nat Neurosci 2, 833–839 (1999).

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