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GABAB(1) receptor subunit isoforms differentially regulate stress resilience.

ABSTRACT: Stressful life events increase the susceptibility to developing psychiatric disorders such as depression; however, many individuals are resilient to such negative effects of stress. Determining the neurobiology underlying this resilience is instrumental to the development of novel and more effective treatments for stress-related psychiatric disorders. GABAB receptors are emerging therapeutic targets for the treatment of stress-related disorders such as depression. These receptors are predominantly expressed as heterodimers of a GABAB(2) subunit with either a GABAB(1a) or a GABAB(1b) subunit. Here we show that mice lacking the GABAB(1b) receptor isoform are more resilient to both early-life stress and chronic psychosocial stress in adulthood, whereas mice lacking GABAB(1a) receptors are more susceptible to stress-induced anhedonia and social avoidance compared with wild-type mice. In addition, increased hippocampal expression of the GABAB(1b) receptor subunit is associated with a depression-like phenotype in the helpless H/Rouen genetic mouse model of depression. Stress resilience in GABAB(1b)(-/-) mice is coupled with increased proliferation and survival of newly born cells in the adult ventral hippocampus and increased stress-induced c-Fos activation in the hippocampus following early-life stress. Taken together, the data suggest that GABAB(1) receptor subunit isoforms differentially regulate the deleterious effects of stress and, thus, may be important therapeutic targets for the treatment of depression.

SUBMITTER: O'Leary OF

PROVIDER: S-EPMC4210293 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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GABAB(1) receptor subunit isoforms differentially regulate stress resilience.

O'Leary Olivia F OF Felice Daniela D Galimberti Stefano S Savignac Hélène M HM Bravo Javier A JA Crowley Tadhg T El Yacoubi Malika M Vaugeois Jean-Marie JM Gassmann Martin M Bettler Bernhard B Dinan Timothy G TG Cryan John F JF

Proceedings of the National Academy of Sciences of the United States of America 20141006 42

Stressful life events increase the susceptibility to developing psychiatric disorders such as depression; however, many individuals are resilient to such negative effects of stress. Determining the neurobiology underlying this resilience is instrumental to the development of novel and more effective treatments for stress-related psychiatric disorders. GABAB receptors are emerging therapeutic targets for the treatment of stress-related disorders such as depression. These receptors are predominant ...[more]

PMID: 25288769

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GABAB(1) receptor subunit isoforms differentially regulate stress resilience.

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GABAB(1) receptor subunit isoforms differentially regulate stress resilience.

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