title: Altered GABAergic and glutamatergic activity within the rat hippocampus and amygdala in rats subjected to repeated corticosterone administration but not restraint stress.
abstract: We investigated the effect of two well characterized preclinical animal models of depression - repeated injections of corticosterone (CORT) and repeated restraint stress - on markers of GABAergic and glutamatergic activity in the hippocampus and amygdala. Stress is an identified risk factor for the onset of major depression, but the neurobiological mechanisms by which stress may produce depressogenic effects are not clear. Rats received one of the following four treatments for 21 consecutive days: daily single CORT injections (40mg/kg), daily single vehicle injections, daily 6h of restraint stress, or daily handling. After the 21-day stress period, all rats were sacrificed and hippocampal and amygdalar tissue was collected and prepared for Western blot analyses. We examined the effect of CORT and restraint stress on glutamate decarboxylase (GAD)-65 and GAD67, as well as the α1, α2, α3, and β2-3 GABA(A) receptor subunits, and the vesicular glutamate transporter (VGLUT)-2. We found that CORT significantly decreased GAD65 and the α2 receptor subunit and increased VGLUT2 within the hippocampus. We also found that CORT decreased GAD67 and the α2 receptor subunit in the amygdala. However, restraint stress had no significant effect on protein expression in either the hippocampus or the amygdala. These findings parallel our previous results showing that repeated CORT injections, but not restraint stress, increase depression-like behavior in rats, and suggest that the depressogenic effects of CORT may be related to alterations in GABAergic and glutamatergic neurotransmission in stress-sensitive regions of the brain.
authors.affiliation: Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5A5.
authors.forename: A L
authors.initials: AL
authors.lastname: Lussier
authors.forename: R
authors.initials: R
authors.lastname: Romay-Tallón
authors.forename: H J
authors.initials: HJ
authors.lastname: Caruncho
authors.forename: L E
authors.initials: LE
authors.lastname: Kalynchuk
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D050599:Vesicular Glutamate Transport Protein 2; D005968:Glutamate Decarboxylase; D003345:Corticosterone