Habituation to stress and dexamethasone suppression in rats with selective basal forebrain cholinergic lesions

Katherine A. Helm, D. R. Ziegler, Michela Gallagher

Research output: Contribution to journalArticle

Abstract

Previous studies suggest a role for basal forebrain cholinergic neurons in enhancing the inhibitory influence of the hippocampus and medial prefrontal cortex (mPFC) on glucocorticoid stress responses mediated by the hypothalamic-pituitary-adrenocortical (HPA) axis. An inhibitory action of the basal forebrain cholinergic (BFC) system may occur through facilitation of stress-related information processing and maintenance of glucocorticoid receptor (GR) expression and negative feedback signaling in these target regions. The current study investigated the possibility that BFC input to the hippocampus contributes to habituation of the glucocorticoid response following repeated exposure to a stressor. Cholinergic lesions were made by microinjections of the immunotoxin 192 IgG-saporin into the medial septum/vertical limb of the diagonal band, and 3 weeks later rats were subjected to six daily sessions of restraint stress. Blood samples taken before, during and after acute stress revealed a significant increase in peak activation and protracted elevation of corticosterone in cholinergic lesioned rats. After 5 days of repeated stress, however, both groups habituated to the stressor, as indicated by similarly low corticosterone profiles throughout both the response and recovery period. Against that habituated background, rats were administered a dexamethasone challenge on day 6, so that feedback status could be examined. Dexamethasone-induced suppression of endogenous corticosterone before, during, and after stress was significantly attenuated in lesioned rats. The profile of dysfunction in glucocorticoid regulation after selective cholinergic lesions in young animals may be relevant to the adrenocortical hyperactivity and negative feedback deficits seen in conditions such as normal aging and Alzheimer's dementia, in which integrity of the basal forebrain cholinergic system is compromised.

Original languageEnglish (US)
Pages (from-to)628-635
Number of pages8
JournalHippocampus
Volume14
Issue number5
DOIs
StatePublished - 2004

Fingerprint

Cholinergic Agents
Dexamethasone
Corticosterone
Glucocorticoids
Hippocampus
Immunotoxins
Cholinergic Neurons
Glucocorticoid Receptors
Microinjections
Prefrontal Cortex
Automatic Data Processing
Basal Forebrain
Alzheimer Disease
Extremities
Maintenance

Keywords

  • Adaptation
  • Corticosterone
  • Glucocorticoid
  • Hippocampus
  • HPA axis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Habituation to stress and dexamethasone suppression in rats with selective basal forebrain cholinergic lesions. / Helm, Katherine A.; Ziegler, D. R.; Gallagher, Michela.

In: Hippocampus, Vol. 14, No. 5, 2004, p. 628-635.

Research output: Contribution to journalArticle

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