Neuroendocrine responses to intravenous infusion of arecoline in patients with Alzheimer's disease

Sanjay Asthana, Kathleen C. Raffaele, Nigel H. Greig, Annamaria Berardi, P. Pearse Morris, Mark B. Schapiro, Stanley I. Rapoport, Marc R. Blackman, Timothy T. Soncrant

Research output: Contribution to journalArticle

Abstract

We have reported that arecoline, a muscarinic receptor agonist replicably enhanced verbal memory in five of nine subjects with Alzheimer's disease (AD). To investigate the mechanism of cognitive improvement, circulating hormone measurements were made during high-dose acute and low-dose chronic intravenous (i.v.) arecoline administration to AD patients. Acute hormone responses were measured during, and for 6 h after, infusion of arecoline 5 mg i.v. over 30 min. Chronic responses were measured in cognitive responders during continuous i.v. infusion of arecoline escalating over 2 weeks (0.5-40 mg/day) and then during a 1 week infusion of the dose optimizing cognition (4-16 mg/day). Acute arecoline administered to 14 subjects produced unpleasant side-effects (e.g. nausea, vomiting), mean adrenocorticotrophic hormone (p=.0006), cortisol (p=.0001) and β-endorphin (p=.0001) levels were elevated. During chronic arecoline treatment, no side-effects occurred and plasma cortisol, adrenocorticotrophic hormone and β-endorphin levels were unchanged in nine subjects overall and in five cognitive responders. Thus, high-dose arecoline activates the hypothalamic-pituitary-adrenal (HPA) axis and may increase other anterior pituitary hormone levels, likely representing a 'stress response', but cognition-enhancing, low doses of arecoline do not produce a glucocorticoid response. Hence, arecoline-induced memory improvement is not due to the induction of 'stress' nor to the elevation of peripheral corticosteroid levels.

Original languageEnglish (US)
Pages (from-to)623-636
Number of pages14
JournalPsychoneuroendocrinology
Volume20
Issue number6
DOIs
StatePublished - 1995

Keywords

  • Alzheimer's disease
  • Arecoline
  • Corticosteroid
  • Hypothalamic-pituitary-adrenal axis
  • Memory
  • Stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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    Asthana, S., Raffaele, K. C., Greig, N. H., Berardi, A., Pearse Morris, P., Schapiro, M. B., Rapoport, S. I., Blackman, M. R., & Soncrant, T. T. (1995). Neuroendocrine responses to intravenous infusion of arecoline in patients with Alzheimer's disease. Psychoneuroendocrinology, 20(6), 623-636. https://doi.org/10.1016/0306-4530(94)00084-N