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 gamma2 subunit was reduced, mainly in hippocampus and cerebral cortex. The gamma2 +/- 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 gamma2 +/- 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.
Crestani
F
F
Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Lorez
M
M
Baer
K
K
Essrich
C
C
Benke
D
D
Laurent
J P
JP
Belzung
C
C
Fritschy
J M
JM
Lüscher
B
B
Mohler
H
H
D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D001362:Avoidance Learning / Q000502:physiology; D003216:Conditioning, Operant; D003463:Cues; D005239:Fear; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid