title: GABAergic circuits and the stress hyporesponsive period in the rat: ontogeny of glutamic acid decarboxylase (GAD) 67 mRNA expression in limbic-hypothalamic stress pathways.
abstract: Development of the hypothalamo-pituitary-adrenocortical (HPA) axis is marked by a diminution in stress responsiveness early in the postnatal period (days 4-14 in the rat). This 'stress hyporesponsive period' (SHRP) is thought to be at least in part centrally mediated. To investigate central mechanisms underlying the SHRP, this study assessed expression of glutamic acid decarboxylase (GAD) 67 in key stress-regulatory regions in the forebrain following acute stress with or without prior maternal deprivation. This isoform of GAD is known to be induced by stress in the adult and is believed to be a major contributor to production of the inhibitory neurotransmitter GABA under stimulated conditions. Expression of GAD67 mRNA was increased in the hippocampus, central amygdala and dorsomedial hypothalamus in pups tested early in the SHRP (day 6) or after its conclusion (day 18). In contrast, restraint caused a down-regulation of GAD67 mRNA in these structures when tested later in the SHRP (day 12). GAD67 mRNA expression was not affected by prior maternal deprivation in these regions. Reduced GABA production in the hippocampus (interneurons) is consistent with enhanced HPA axis inhibition, whereas reduced amygdalar expression predicts impaired stress excitation. Expression of GAD67 mRNA in the bed nucleus of the stria terminalis (BST) was minimally affected by acute restraint or maternal deprivation during the SHRP. However, older animals showed down-regulation of basal expression following maternal deprivation and substantial GAD67 mRNA up-regulation in both deprived and non-deprived groups following acute restraint. In contrast, non-responsiveness of the BST during the SHRP suggests either that BST GABA circuits are not actively engaged by stressors during this period or that circuits regulating BST GAD67 production are not yet in place. Overall, the data implicate forebrain GABA circuits in inhibition of HPA axis activity during the SHRP.
authors.affiliation: Department of Biology, University of Delaware, Newark, DE 19716-2577, USA.
authors.forename: Gersham
authors.initials: G
authors.lastname: Dent
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Choi
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
authors.forename: Seymour
authors.initials: S
authors.lastname: Levine
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics*; D007031:Hypothalamus / Q000201:enzymology / Q000503:physiopathology*; D007527:Isoenzymes / Q000235:genetics*; D008032:Limbic System / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D008426:Maternal Deprivation; D009433:Neural Inhibition; D009434:Neural Pathways / Q000503:physiopathology; D016548:Prosencephalon / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012686:Septal Nuclei / Q000503:physiopathology; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D014018:Tissue Distribution; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1