Drug discrimination analysis of endogenous neuroactive steroids in rats

Nancy A. Ator, Kathleen (Kathy) Grant, Robert H. Purdy, Steven M. Paul, Roland R. Griffiths

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Rats were trained in a two-lever procedure to discriminate either pentobarbital (10 mg/kg), ethanol (1.5 g/kg), diazepam (1 mg/kg), or lorazepam (1 mg/kg) from the no-drug condition. Consistent with previous reports, rats in the pentobarbital, ethanol, and diazepam training conditions all showed complete dose-dependent generalization to pentobarbital under test conditions, but rats trained to discriminate lorazepam did not. Administration of the neuroactive steroids 3α, 21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC) and 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) also produced complete generalization in rats trained to discriminate pentobarbital, ethanol, and diazepam, but not in rats trained to discriminate lorazepam. These results further indicate the specificity of the lorazepam training condition and are consistent with neurochemical data indicating that these neuroactive steroids are similar to barbiturates in modulating γ-aminobutyric acid (GABA)A receptors. In the context of previous data, the results from the four training groups suggest that the discriminative-stimulus effects of the neuroactive steroids are sedative/anxiolytic in nature and probably mediated through a non-benzodiazepine GABAA site.

Original languageEnglish (US)
Pages (from-to)237-243
Number of pages7
JournalEuropean Journal of Pharmacology
Volume241
Issue number2-3
DOIs
StatePublished - Sep 14 1993
Externally publishedYes

Fingerprint

Lorazepam
Pentobarbital
Steroids
Diazepam
Ethanol
Pharmaceutical Preparations
Aminobutyrates
Barbiturates
Anti-Anxiety Agents
GABA-A Receptors
Hypnotics and Sedatives
pregnane-20-one

Keywords

  • Behaviour
  • Benzodiazepines
  • Drug discrimination
  • Ethanol
  • Neuroactive steroids
  • Pentobarbital

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Drug discrimination analysis of endogenous neuroactive steroids in rats. / Ator, Nancy A.; Grant, Kathleen (Kathy); Purdy, Robert H.; Paul, Steven M.; Griffiths, Roland R.

In: European Journal of Pharmacology, Vol. 241, No. 2-3, 14.09.1993, p. 237-243.

Research output: Contribution to journalArticle

Ator, Nancy A. ; Grant, Kathleen (Kathy) ; Purdy, Robert H. ; Paul, Steven M. ; Griffiths, Roland R. / Drug discrimination analysis of endogenous neuroactive steroids in rats. In: European Journal of Pharmacology. 1993 ; Vol. 241, No. 2-3. pp. 237-243.
@article{b617b2e96f514e4187f5de47e598e724,
title = "Drug discrimination analysis of endogenous neuroactive steroids in rats",
abstract = "Rats were trained in a two-lever procedure to discriminate either pentobarbital (10 mg/kg), ethanol (1.5 g/kg), diazepam (1 mg/kg), or lorazepam (1 mg/kg) from the no-drug condition. Consistent with previous reports, rats in the pentobarbital, ethanol, and diazepam training conditions all showed complete dose-dependent generalization to pentobarbital under test conditions, but rats trained to discriminate lorazepam did not. Administration of the neuroactive steroids 3α, 21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC) and 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) also produced complete generalization in rats trained to discriminate pentobarbital, ethanol, and diazepam, but not in rats trained to discriminate lorazepam. These results further indicate the specificity of the lorazepam training condition and are consistent with neurochemical data indicating that these neuroactive steroids are similar to barbiturates in modulating γ-aminobutyric acid (GABA)A receptors. In the context of previous data, the results from the four training groups suggest that the discriminative-stimulus effects of the neuroactive steroids are sedative/anxiolytic in nature and probably mediated through a non-benzodiazepine GABAA site.",
keywords = "Behaviour, Benzodiazepines, Drug discrimination, Ethanol, Neuroactive steroids, Pentobarbital",
author = "Ator, {Nancy A.} and Grant, {Kathleen (Kathy)} and Purdy, {Robert H.} and Paul, {Steven M.} and Griffiths, {Roland R.}",
year = "1993",
month = "9",
day = "14",
doi = "10.1016/0014-2999(93)90208-Y",
language = "English (US)",
volume = "241",
pages = "237--243",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Drug discrimination analysis of endogenous neuroactive steroids in rats

AU - Ator, Nancy A.

AU - Grant, Kathleen (Kathy)

AU - Purdy, Robert H.

AU - Paul, Steven M.

AU - Griffiths, Roland R.

PY - 1993/9/14

Y1 - 1993/9/14

N2 - Rats were trained in a two-lever procedure to discriminate either pentobarbital (10 mg/kg), ethanol (1.5 g/kg), diazepam (1 mg/kg), or lorazepam (1 mg/kg) from the no-drug condition. Consistent with previous reports, rats in the pentobarbital, ethanol, and diazepam training conditions all showed complete dose-dependent generalization to pentobarbital under test conditions, but rats trained to discriminate lorazepam did not. Administration of the neuroactive steroids 3α, 21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC) and 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) also produced complete generalization in rats trained to discriminate pentobarbital, ethanol, and diazepam, but not in rats trained to discriminate lorazepam. These results further indicate the specificity of the lorazepam training condition and are consistent with neurochemical data indicating that these neuroactive steroids are similar to barbiturates in modulating γ-aminobutyric acid (GABA)A receptors. In the context of previous data, the results from the four training groups suggest that the discriminative-stimulus effects of the neuroactive steroids are sedative/anxiolytic in nature and probably mediated through a non-benzodiazepine GABAA site.

AB - Rats were trained in a two-lever procedure to discriminate either pentobarbital (10 mg/kg), ethanol (1.5 g/kg), diazepam (1 mg/kg), or lorazepam (1 mg/kg) from the no-drug condition. Consistent with previous reports, rats in the pentobarbital, ethanol, and diazepam training conditions all showed complete dose-dependent generalization to pentobarbital under test conditions, but rats trained to discriminate lorazepam did not. Administration of the neuroactive steroids 3α, 21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC) and 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) also produced complete generalization in rats trained to discriminate pentobarbital, ethanol, and diazepam, but not in rats trained to discriminate lorazepam. These results further indicate the specificity of the lorazepam training condition and are consistent with neurochemical data indicating that these neuroactive steroids are similar to barbiturates in modulating γ-aminobutyric acid (GABA)A receptors. In the context of previous data, the results from the four training groups suggest that the discriminative-stimulus effects of the neuroactive steroids are sedative/anxiolytic in nature and probably mediated through a non-benzodiazepine GABAA site.

KW - Behaviour

KW - Benzodiazepines

KW - Drug discrimination

KW - Ethanol

KW - Neuroactive steroids

KW - Pentobarbital

UR - http://www.scopus.com/inward/record.url?scp=0027205543&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027205543&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(93)90208-Y

DO - 10.1016/0014-2999(93)90208-Y

M3 - Article

C2 - 7902289

AN - SCOPUS:0027205543

VL - 241

SP - 237

EP - 243

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -