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Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: effect of ethanol training dose and dosing procedure.
J Pharmacol Exp Ther. 1999 Apr; 289(1):405-11.JP

Abstract

A number of endogenous steroids exhibit rapid, nongenomic effects on the central nervous system and are called neuroactive steroids. The rapid mechanisms of action include modulation of gamma-aminobutyric acid type A (GABAA) and N-methyl-D-aspartate (NMDA) receptors, which are two receptors implicated in the behavioral effects of ethanol. It was hypothesized that neuroactive steroids that positively modulate GABAA receptors or negatively modulate NMDA receptors, analogous to the actions of ethanol, would produce discriminative stimulus effects similar to ethanol. Two groups of male Long-Evans rats (n = 6-8/group) were trained to discriminate between 1.0 or 2.0 g/kg ethanol (i.g.) and water (i.g.). The neuroactive steroids allopregnanolone, pregnanolone, epipregnanolone, allotetrahydrodeoxycorticosterone, pregnanolone sulfate, epipregnanolone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate, pregnenolone, and pregnenolone sulfate (PS), all administered i.p., were tested for substitution with acute and cumulative dosing procedures (n = 4-8/steroid). The GABAA-positive modulatory steroids allopregnanolone, pregnanolone, and allotetrahydrodeoxycorticosterone substituted for ethanol, as did the low-efficacy steroid 3beta,5beta-P. GABAA-negative modulators, such as dehydroepiandrosterone sulfate and PS, and all of the NMDA modulators tested, including PS, pregnanolone sulfate, and epipregnanolone sulfate, did not substitute for ethanol. These results show that certain endogenously occurring neuroactive steroids produce discriminative stimulus effects similar to those of ethanol.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10087031

Citation

Bowen, C A., et al. "Ethanol-like Discriminative Stimulus Effects of Endogenous Neuroactive Steroids: Effect of Ethanol Training Dose and Dosing Procedure." The Journal of Pharmacology and Experimental Therapeutics, vol. 289, no. 1, 1999, pp. 405-11.
Bowen CA, Purdy RH, Grant KA. Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: effect of ethanol training dose and dosing procedure. J Pharmacol Exp Ther. 1999;289(1):405-11.
Bowen, C. A., Purdy, R. H., & Grant, K. A. (1999). Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: effect of ethanol training dose and dosing procedure. The Journal of Pharmacology and Experimental Therapeutics, 289(1), 405-11.
Bowen CA, Purdy RH, Grant KA. Ethanol-like Discriminative Stimulus Effects of Endogenous Neuroactive Steroids: Effect of Ethanol Training Dose and Dosing Procedure. J Pharmacol Exp Ther. 1999;289(1):405-11. PubMed PMID: 10087031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: effect of ethanol training dose and dosing procedure. AU - Bowen,C A, AU - Purdy,R H, AU - Grant,K A, PY - 1999/3/23/pubmed PY - 1999/3/23/medline PY - 1999/3/23/entrez SP - 405 EP - 11 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 289 IS - 1 N2 - A number of endogenous steroids exhibit rapid, nongenomic effects on the central nervous system and are called neuroactive steroids. The rapid mechanisms of action include modulation of gamma-aminobutyric acid type A (GABAA) and N-methyl-D-aspartate (NMDA) receptors, which are two receptors implicated in the behavioral effects of ethanol. It was hypothesized that neuroactive steroids that positively modulate GABAA receptors or negatively modulate NMDA receptors, analogous to the actions of ethanol, would produce discriminative stimulus effects similar to ethanol. Two groups of male Long-Evans rats (n = 6-8/group) were trained to discriminate between 1.0 or 2.0 g/kg ethanol (i.g.) and water (i.g.). The neuroactive steroids allopregnanolone, pregnanolone, epipregnanolone, allotetrahydrodeoxycorticosterone, pregnanolone sulfate, epipregnanolone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate, pregnenolone, and pregnenolone sulfate (PS), all administered i.p., were tested for substitution with acute and cumulative dosing procedures (n = 4-8/steroid). The GABAA-positive modulatory steroids allopregnanolone, pregnanolone, and allotetrahydrodeoxycorticosterone substituted for ethanol, as did the low-efficacy steroid 3beta,5beta-P. GABAA-negative modulators, such as dehydroepiandrosterone sulfate and PS, and all of the NMDA modulators tested, including PS, pregnanolone sulfate, and epipregnanolone sulfate, did not substitute for ethanol. These results show that certain endogenously occurring neuroactive steroids produce discriminative stimulus effects similar to those of ethanol. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10087031/Ethanol_like_discriminative_stimulus_effects_of_endogenous_neuroactive_steroids:_effect_of_ethanol_training_dose_and_dosing_procedure_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10087031 DB - PRIME DP - Unbound Medicine ER -