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

doi:10.1016/0006-3223(86)90243-X

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 journal › Article › peer-review

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Abstract

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 language	English (US)
Pages (from-to)	775-786
Number of pages	12
Journal	Biological Psychiatry
Volume	21
Issue number	8-9
DOIs	https://doi.org/10.1016/0006-3223(86)90243-X
State	Published - Jul 1986
Externally published	Yes

ASJC Scopus subject areas

Biological Psychiatry

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10.1016/0006-3223(86)90243-X

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@article{2d179e374b7540b7b044e184c1ae25f2,

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

abstract = "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.",

author = "Downs, {Nancy S.} and Britton, {Karen T.} and Gibbs, {Daniel M.} and Koob, {George F.} and Swerdlow, {Neal R.}",

note = "Funding Information: From the School of Medicine (N.S.D.), the Department of Psychiatry (K.T.B.), the Depattment of Reproductive Medicine (D.M.G.), and the Department of Neuroscience and M.S.T. Program (N.R.S.), University of California, San Diego, and the Division of Preclinical Neuroscience and Endocrinology (G.F.K.), Scripps Clinic and Research Foundation, La Jolla, CA. Supported in part by NIH, National Research Service Award PHSGM 07198-10, NM Gram PO1 AM 26741-0491, and NIAAA AAO6420-01. This is publication 4016BCR from the Research Institute of Scripps Clinic, La Jolla, CA. Address reprint requests to Dr. George F. Koob, Division of Preclinical Neuroscience and Endocrinology, Scripps Clinic and Research Foundation; 10666 North Torrey Pines Road, La Jolla, CA 92037. Received September 17, 1985; revised January 21, 1986.",

year = "1986",

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doi = "10.1016/0006-3223(86)90243-X",

language = "English (US)",

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journal = "Biological Psychiatry",

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T1 - Supersensitive endocrine response to physostigmine in dopamine-depleted rats

T2 - A model of depression?

AU - Downs, Nancy S.

AU - Britton, Karen T.

AU - Gibbs, Daniel M.

AU - Koob, George F.

AU - Swerdlow, Neal R.

N1 - Funding Information: From the School of Medicine (N.S.D.), the Department of Psychiatry (K.T.B.), the Depattment of Reproductive Medicine (D.M.G.), and the Department of Neuroscience and M.S.T. Program (N.R.S.), University of California, San Diego, and the Division of Preclinical Neuroscience and Endocrinology (G.F.K.), Scripps Clinic and Research Foundation, La Jolla, CA. Supported in part by NIH, National Research Service Award PHSGM 07198-10, NM Gram PO1 AM 26741-0491, and NIAAA AAO6420-01. This is publication 4016BCR from the Research Institute of Scripps Clinic, La Jolla, CA. Address reprint requests to Dr. George F. Koob, Division of Preclinical Neuroscience and Endocrinology, Scripps Clinic and Research Foundation; 10666 North Torrey Pines Road, La Jolla, CA 92037. Received September 17, 1985; revised January 21, 1986.

PY - 1986/7

Y1 - 1986/7

N2 - 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.

AB - 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.

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JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 8-9

ER -

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

Abstract

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