Supersensitive endocrine response to physostigmine in dopamine-depleted rats: A model of depression?

Nancy S. Downs, Karen T. Britton, Daniel M. Gibbs, George F. Koob, Neal R. Swerdlow

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Depressed patients exhibit an abnormal "supersensitive" increase in the plasma concentration of several pituitary hormones following intravenous injection of the acetyl cholinesterase inhibitor physostigmine (PHY). In the present study, we examined the effects of PHY treatments on the plasma concentrations of prolactin (PRL) and adrenocorticotrophic hormone (ACTH) in the rat. Physostigmine (0-0.6 mg/kg, s.c.) produced a dose-dependent increase in PRL and ACTH immunoreactivity in unoperated animals. Neurotoxin-induced depletion of brain dopamine (DA) or norepinephrine (NE) did not significantly alter baseline plasma PRL or ACTH values. Following depletion of brain DA, but not NE, animals exhibited a "supersensitive" increase in plasma ACTH values, which was evidenced by a sixfold left shift in the dose-response properties of PHY. These results suggest that there are intriguing parallels between the abnormal endocrine response to PHY demonstrated by depressed patients and that demonstrated by rats following depletion of central nervous system (CNS) DA levels.

Original languageEnglish (US)
Pages (from-to)775-786
Number of pages12
JournalBiological Psychiatry
Issue number8-9
StatePublished - Jul 1986
Externally publishedYes

ASJC Scopus subject areas

  • Biological Psychiatry


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