title: Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.
abstract: Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Laboratory of Neuropsychopharmacology and Psychoneuroimmunology, Hayyan Research Institute, University of Tabriz, Tabriz, Iran. Electronic address: aa.salari@yahoo.com.
authors.forename: Ali-Akbar
authors.initials: AA
authors.lastname: Salari
authors.affiliation: Department of Microbiology, Faculty of Sciences, Karaj Branch, Islamic Azad University, Alborz, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Bakhtiari
authors.affiliation: Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000378:metabolism*; D001640:Bicuculline; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009118:Muscimol; D011963:Receptors, GABA-A / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism; D013997:Time Factors
chemical_list: D011963:Receptors, GABA-A; D009118:Muscimol; D003345:Corticosterone; D001640:Bicuculline
keywords: Anxiety; Bicuculline; Depression; Early life; HPA axis; Muscimol