Endogenous GABA levels were altered in mice by targeting the two isoforms of glutamic acid dehydrogenase (GAD) responsible for the synthesis of GABA. Mice lacking GAD67, which is thought to be responsible for maintenance of basal GABA levels, produced a prenatal lethal phenotype. Deletion of the GAD65 gene, thought to be activated in response to high endogenous GABA demand, reduced GABA levels, was associated with a lower rate of lethality than the GAD67 mutant mice, and exhibited an increase in anxiety-like behavior in the elevated zero maze and open field tests.22

Deletion of the b2 subunit gene of the GABAa receptor decreased the total number of GABAa receptors in the brain, but did not produce any clear anxiety-related phenotype.23 Mice deficient in both splice variants of the g2 subunit (g2S, g2L) of the GABAa receptor were insensitive to either the behavioral or electrophysiological effects of benzodiazepines.24 Homozygous mutants failed to survive past postnatal day 18, and behavioral testing with heterozygote g2 mutants showed anxiogenic-like behavior in the open field, elevated plus maze (EPM), and light/dark box tests.24 Although the g2 subunit knockout mice showed some increases in anxiety-like behavior, transgenic mice overexpressing either the g2S or g2L subunits of the GABAA receptor failed to exhibit any anxiety-like phenotype when compared to the responses of their wild-type littermate controls.25

How To Win Your War Against Anxiety Disorders

How To Win Your War Against Anxiety Disorders

Tips And Tricks For Relieving Anxiety... Fast Everyone feels anxious sometimes. Whether work is getting to us or we're simply having hard time managing all that we have to do, we can feel overwhelmed and worried that we might not be able to manage it all. When these feelings hit, we don't have to suffer. By taking some simple steps, you can begin to create a calmer attitude, one that not only helps you feel better, but one that allows you the chance to make better decisions about what you need to do next.

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