title: Differential susceptibility to extinction-induced despair and age-dependent alterations in the hypothalamic-pituitary-adrenal axis and neurochemical parameters.
abstract: Clinical studies point to structural differences in the neurobiological mechanisms underlying early versus late onset of depression. However, studies examining the neuropathology of depressive-like behavior induced in the aged rodent are sparse. Extinction of learned behavior induces be- havioral 'despair', and is held to provide a conceptual and empirical model of human depression resulting from the withdrawal of reinforcement. We tested whether the neuroendocrinological and chemical concomitants of susceptibility to extinction-induced despair in aged animals differed from adult ones. Following the withholding of reinforcement (extinction of escape from a water maze), a number of aged and adult rats are prone to develop depressive-like behavior, i.e. immobility. Analysis of hypothalamus-pituitary-adrenal (HPA) axis markers revealed an increase in the mineralocorticoid/glucocorticoid receptor (MR/GR) mRNA ratio in the CA1 region of the hippocampus in aged and adult despair animals; however, in dependence on age, divergent changes contributed to the enhanced ratio. While aged despair rats had less GR mRNA, adult despair rats had more MR mRNA. Furthermore, age- and despair-related interactions with hippocampal and cortical steroid receptor co-activators and neurotransmitter contents in diverse brain areas were found. For instance, adult despair rats had an increased, and aged despair rats a decreased, DOPAC/dopamine turnover compared to the respective non-despair group. These results show that neurobiological underpinnings of depression in the aged differ from those of adults, and underline the importance of investigating age-related alterations in HPA axis dynamics in conjunction with neurotransmitter systems to advance our knowledge about neuronal mechanisms of late-life and/or late-onset depression.
authors.affiliation: Institute of Physiological Psychology, University of Düsseldorf, Düsseldorf, Germany. topic@uni-duesseldorf.de
authors.forename: Bianca
authors.initials: B
authors.lastname: Topic
authors.forename: Melly S
authors.initials: MS
authors.lastname: Oitzl
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
authors.forename: Maria A
authors.initials: MA
authors.lastname: de Souza Silva
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D003863:Depression / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D005108:Extinction, Psychological; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012054:Reinforcement, Psychology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine