GABA homeostasis contributes to the developmental programming of anxiety-related behavior

Brain Research
Amaicha Mara DepinoCornelius Gross

Abstract

During development, when inhibitory and excitatory synapses are formed and refined, homeostatic mechanisms act to adjust inhibitory input in order to maintain neural activity within a normal range. As the brain matures, synaptogenesis slows and a relatively stable level of inhibition is achieved. Deficits in inhibitory neurotransmission are associated with increased anxiety-related behavior and drugs that potentiate GABA function, the major inhibitory neurotransmitter in the brain, are effective anxiolytics. These observations raise the possibility that transient perturbations in the activity of neural circuits during development might induce compensatory changes in inhibition that could persist into adulthood and contribute to changes in anxiety-related behavior. To test this hypothesis, we treated mice continuously during the major period of forebrain synaptogenesis (P14-28) with the GABA-A receptor positive modulator diazepam and assessed anxiety-related behavior in adulthood. Control experiments confirmed anxiolytic effects of the drug following one day of treatment and the development of tolerance following two weeks of treatment. When tested in adulthood, one month after the end of treatment, diazepam-treated mice exhibit...Continue Reading

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Dec 17, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Douglas O FrostBryan Kolb
Sep 7, 2012·Genes, Brain, and Behavior·M CampolongoA M Depino
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Jun 28, 2018·Molecular Autism·Marcos CampolongoAmaicha Mara Depino
Jul 31, 2020·Behavioural Brain Research·Lorrane Kelle MoreiraElson Alves Costa

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