The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators

Kristen L. Green; Alexey V. Azarov; Kendall T. Szeliga; Robert H. Purdy; Kathleen A. Grant

doi:10.1016/S0091-3057(99)00057-X

The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators

Kristen L. Green
, Alexey V. Azarov
, Kendall T. Szeliga
, Robert H. Purdy
, Kathleen A. Grant

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Previous studies showed that sensitivity to the ethanol-like discriminative stimulus effects of allopregnanolone and ethanol are enhanced during the luteal phase of the menstrual cycle when progesterone levels peak in monkeys trained to discriminate 1.0 g/kg ethanol. The present study further explored the influence of the menstrual cycle phase on the discriminative stimulus effects of ethanol, allopregnanolone, and midazolam. Female adult cynomolgus monkeys (Macaca fascicularis) were trained to discriminate 1.0 g/kg ethanol (n = 3) or 2.0 g/kg ethanol (n = 4) (20% w/v; IG) from water (IG). A cumulative dosing procedure was used to test discriminative stimulus effects of ethanol (0.5-2.5 g/kg; IG) and the ethanol-like discriminative stimulus effects of allopregnanolone (0.1-1.0 mg/kg; IV) or midazolam (1.0-17 mg/kg; IG) during the follicular vs. luteal phase of the menstrual cycle. In the 2.0-g/kg group, sensitivity to the ethanol- like effects of allopregnanolone was increased during the luteal vs. follicular phase in two of three monkeys. In contrast, average sensitivity to ethanol was not different in the luteal compared to the follicular phase in the 2.0-g/kg group. Finally, there was no difference in sensitivity to midazolam between the follicular and luteal phases in monkeys trained with either 2.0 g/kg or 1.0 g/kg ethanol. Overall, the ethanol-like discriminative stimulus effects of midazolam are not sensitive to the menstrual cycle phase. In addition, there was less influence of the menstrual cycle phase on allopregnanolone and ethanol sensitivity in a 2.0-g/kg compared to a 1.0-g/kg ethanol training dose. Copyright (C) 1999 Elsevier Science Inc.

Original language	English (US)
Pages (from-to)	379-383
Number of pages	5
Journal	Pharmacology Biochemistry and Behavior
Volume	64
Issue number	2
DOIs	https://doi.org/10.1016/S0091-3057(99)00057-X
State	Published - Oct 1999
Externally published	Yes

Funding

Care and treatment of the subjects used in this study were in accord with state and federal guidelines. The experimental protocol was approved by the Wake Forest University Animal Care and Use Committee. This research was supported in part by grants from the National Institute on Alcohol Abuse and Alcoholism RO1 AA10009, T32 AA07565, and P5O AA06420. Midazolam was provided by Dr. P. Weber of Hoffmann–LaRoche Ltd. (Basel, France). Serum progesterone levels were determined at the Assay Services of Yerkes Regional Primate Research Center of Emory University under the direction of Dr. M. Wilson.

Funders	Funder number
National Institute of Alcohol Abuse and Alcoholism	P5O AA06420, T32 AA07565, R01AA010009

Keywords

3α-Hydroxy-5α-pregnan-20-one
Allopregnanolone
Cynomolgus monkeys
Drug discrimination
Ethanol
Menstrual cycle
Midazolam
Progesterone

ASJC Scopus subject areas

Biochemistry
Toxicology
Pharmacology
Clinical Biochemistry
Biological Psychiatry
Behavioral Neuroscience

Access to Document

10.1016/S0091-3057(99)00057-X

Cite this

@article{6550e1e2addd46d38d2a4871a575fd88,

title = "The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators",

abstract = "Previous studies showed that sensitivity to the ethanol-like discriminative stimulus effects of allopregnanolone and ethanol are enhanced during the luteal phase of the menstrual cycle when progesterone levels peak in monkeys trained to discriminate 1.0 g/kg ethanol. The present study further explored the influence of the menstrual cycle phase on the discriminative stimulus effects of ethanol, allopregnanolone, and midazolam. Female adult cynomolgus monkeys (Macaca fascicularis) were trained to discriminate 1.0 g/kg ethanol (n = 3) or 2.0 g/kg ethanol (n = 4) (20\% w/v; IG) from water (IG). A cumulative dosing procedure was used to test discriminative stimulus effects of ethanol (0.5-2.5 g/kg; IG) and the ethanol-like discriminative stimulus effects of allopregnanolone (0.1-1.0 mg/kg; IV) or midazolam (1.0-17 mg/kg; IG) during the follicular vs. luteal phase of the menstrual cycle. In the 2.0-g/kg group, sensitivity to the ethanol- like effects of allopregnanolone was increased during the luteal vs. follicular phase in two of three monkeys. In contrast, average sensitivity to ethanol was not different in the luteal compared to the follicular phase in the 2.0-g/kg group. Finally, there was no difference in sensitivity to midazolam between the follicular and luteal phases in monkeys trained with either 2.0 g/kg or 1.0 g/kg ethanol. Overall, the ethanol-like discriminative stimulus effects of midazolam are not sensitive to the menstrual cycle phase. In addition, there was less influence of the menstrual cycle phase on allopregnanolone and ethanol sensitivity in a 2.0-g/kg compared to a 1.0-g/kg ethanol training dose. Copyright (C) 1999 Elsevier Science Inc.",

keywords = "3α-Hydroxy-5α-pregnan-20-one, Allopregnanolone, Cynomolgus monkeys, Drug discrimination, Ethanol, Menstrual cycle, Midazolam, Progesterone",

author = "Green, \{Kristen L.\} and Azarov, \{Alexey V.\} and Szeliga, \{Kendall T.\} and Purdy, \{Robert H.\} and Grant, \{Kathleen A.\}",

note = "Funding Information: Care and treatment of the subjects used in this study were in accord with state and federal guidelines. The experimental protocol was approved by the Wake Forest University Animal Care and Use Committee. This research was supported in part by grants from the National Institute on Alcohol Abuse and Alcoholism RO1 AA10009, T32 AA07565, and P5O AA06420. Midazolam was provided by Dr. P. Weber of Hoffmann–LaRoche Ltd. (Basel, France). Serum progesterone levels were determined at the Assay Services of Yerkes Regional Primate Research Center of Emory University under the direction of Dr. M. Wilson.",

year = "1999",

month = oct,

doi = "10.1016/S0091-3057(99)00057-X",

language = "English (US)",

volume = "64",

pages = "379--383",

journal = "Pharmacology Biochemistry and Behavior",

issn = "0091-3057",

publisher = "Elsevier Inc.",

number = "2",

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T1 - The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators

AU - Green, Kristen L.

AU - Azarov, Alexey V.

AU - Szeliga, Kendall T.

AU - Purdy, Robert H.

AU - Grant, Kathleen A.

N1 - Funding Information: Care and treatment of the subjects used in this study were in accord with state and federal guidelines. The experimental protocol was approved by the Wake Forest University Animal Care and Use Committee. This research was supported in part by grants from the National Institute on Alcohol Abuse and Alcoholism RO1 AA10009, T32 AA07565, and P5O AA06420. Midazolam was provided by Dr. P. Weber of Hoffmann–LaRoche Ltd. (Basel, France). Serum progesterone levels were determined at the Assay Services of Yerkes Regional Primate Research Center of Emory University under the direction of Dr. M. Wilson.

PY - 1999/10

Y1 - 1999/10

N2 - Previous studies showed that sensitivity to the ethanol-like discriminative stimulus effects of allopregnanolone and ethanol are enhanced during the luteal phase of the menstrual cycle when progesterone levels peak in monkeys trained to discriminate 1.0 g/kg ethanol. The present study further explored the influence of the menstrual cycle phase on the discriminative stimulus effects of ethanol, allopregnanolone, and midazolam. Female adult cynomolgus monkeys (Macaca fascicularis) were trained to discriminate 1.0 g/kg ethanol (n = 3) or 2.0 g/kg ethanol (n = 4) (20% w/v; IG) from water (IG). A cumulative dosing procedure was used to test discriminative stimulus effects of ethanol (0.5-2.5 g/kg; IG) and the ethanol-like discriminative stimulus effects of allopregnanolone (0.1-1.0 mg/kg; IV) or midazolam (1.0-17 mg/kg; IG) during the follicular vs. luteal phase of the menstrual cycle. In the 2.0-g/kg group, sensitivity to the ethanol- like effects of allopregnanolone was increased during the luteal vs. follicular phase in two of three monkeys. In contrast, average sensitivity to ethanol was not different in the luteal compared to the follicular phase in the 2.0-g/kg group. Finally, there was no difference in sensitivity to midazolam between the follicular and luteal phases in monkeys trained with either 2.0 g/kg or 1.0 g/kg ethanol. Overall, the ethanol-like discriminative stimulus effects of midazolam are not sensitive to the menstrual cycle phase. In addition, there was less influence of the menstrual cycle phase on allopregnanolone and ethanol sensitivity in a 2.0-g/kg compared to a 1.0-g/kg ethanol training dose. Copyright (C) 1999 Elsevier Science Inc.

AB - Previous studies showed that sensitivity to the ethanol-like discriminative stimulus effects of allopregnanolone and ethanol are enhanced during the luteal phase of the menstrual cycle when progesterone levels peak in monkeys trained to discriminate 1.0 g/kg ethanol. The present study further explored the influence of the menstrual cycle phase on the discriminative stimulus effects of ethanol, allopregnanolone, and midazolam. Female adult cynomolgus monkeys (Macaca fascicularis) were trained to discriminate 1.0 g/kg ethanol (n = 3) or 2.0 g/kg ethanol (n = 4) (20% w/v; IG) from water (IG). A cumulative dosing procedure was used to test discriminative stimulus effects of ethanol (0.5-2.5 g/kg; IG) and the ethanol-like discriminative stimulus effects of allopregnanolone (0.1-1.0 mg/kg; IV) or midazolam (1.0-17 mg/kg; IG) during the follicular vs. luteal phase of the menstrual cycle. In the 2.0-g/kg group, sensitivity to the ethanol- like effects of allopregnanolone was increased during the luteal vs. follicular phase in two of three monkeys. In contrast, average sensitivity to ethanol was not different in the luteal compared to the follicular phase in the 2.0-g/kg group. Finally, there was no difference in sensitivity to midazolam between the follicular and luteal phases in monkeys trained with either 2.0 g/kg or 1.0 g/kg ethanol. Overall, the ethanol-like discriminative stimulus effects of midazolam are not sensitive to the menstrual cycle phase. In addition, there was less influence of the menstrual cycle phase on allopregnanolone and ethanol sensitivity in a 2.0-g/kg compared to a 1.0-g/kg ethanol training dose. Copyright (C) 1999 Elsevier Science Inc.

KW - 3α-Hydroxy-5α-pregnan-20-one

KW - Allopregnanolone

KW - Cynomolgus monkeys

KW - Drug discrimination

KW - Ethanol

KW - Menstrual cycle

KW - Midazolam

KW - Progesterone

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U2 - 10.1016/S0091-3057(99)00057-X

DO - 10.1016/S0091-3057(99)00057-X

M3 - Article

C2 - 10515317

AN - SCOPUS:0032878768

SN - 0091-3057

VL - 64

SP - 379

EP - 383

JO - Pharmacology Biochemistry and Behavior

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IS - 2

ER -

The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators

Abstract

Funding

Keywords

ASJC Scopus subject areas

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