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Overlapping, but not identical, discriminative stimulus effects of the neuroactive steroid pregnanolone and ethanol.
Pharmacol Biochem Behav. 2008 May; 89(3):473-9.PB

Abstract

Many behavioral effects of neuroactive steroids are mediated by GABA(A) receptors; however, other receptors might be involved. Ethanol has a complex mechanism of action, and many of the same receptors have been implicated in the effects of neuroactive steroids and ethanol. The goal of this study was to determine whether actions of neuroactive steroids and ethanol at multiple receptors result in similar discriminative stimulus effects. Rats discriminated 5.6 mg/kg of pregnanolone while responding under a fixed-ratio 20 schedule of food presentation. Pregnanolone, flunitrazepam and pentobarbital produced >80% pregnanolone-lever responding. In contrast, neither morphine nor the negative GABA(A) modulator beta-CCE substituted for pregnanolone up to doses that markedly decreased response rates. Ethanol substituted only in some rats; in other rats, ethanol produced <20% pregnanolone-lever responding up to rate-decreasing doses. Thus, substitution of positive GABA(A) modulators, and not morphine or beta-CCE, for pregnanolone in all rats suggests that positive modulation of GABA(A) receptors is important in the discriminative stimulus effects of pregnanolone. Although pregnanolone might have actions at other receptors, in addition to actions at GABA(A) receptors, substitution of ethanol for pregnanolone only in some rats suggests that the mechanisms of action of pregnanolone and ethanol overlap, but are not identical.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, USA. gerak@uthscsa.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18328551

Citation

Gerak, Lisa R., et al. "Overlapping, but Not Identical, Discriminative Stimulus Effects of the Neuroactive Steroid Pregnanolone and Ethanol." Pharmacology, Biochemistry, and Behavior, vol. 89, no. 3, 2008, pp. 473-9.
Gerak LR, Moerschbaecher JM, Winsauer PJ. Overlapping, but not identical, discriminative stimulus effects of the neuroactive steroid pregnanolone and ethanol. Pharmacol Biochem Behav. 2008;89(3):473-9.
Gerak, L. R., Moerschbaecher, J. M., & Winsauer, P. J. (2008). Overlapping, but not identical, discriminative stimulus effects of the neuroactive steroid pregnanolone and ethanol. Pharmacology, Biochemistry, and Behavior, 89(3), 473-9. https://doi.org/10.1016/j.pbb.2008.02.005
Gerak LR, Moerschbaecher JM, Winsauer PJ. Overlapping, but Not Identical, Discriminative Stimulus Effects of the Neuroactive Steroid Pregnanolone and Ethanol. Pharmacol Biochem Behav. 2008;89(3):473-9. PubMed PMID: 18328551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overlapping, but not identical, discriminative stimulus effects of the neuroactive steroid pregnanolone and ethanol. AU - Gerak,Lisa R, AU - Moerschbaecher,Joseph M, AU - Winsauer,Peter J, Y1 - 2008/02/11/ PY - 2007/08/29/received PY - 2008/01/15/revised PY - 2008/02/04/accepted PY - 2008/3/11/pubmed PY - 2008/5/21/medline PY - 2008/3/11/entrez SP - 473 EP - 9 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 89 IS - 3 N2 - Many behavioral effects of neuroactive steroids are mediated by GABA(A) receptors; however, other receptors might be involved. Ethanol has a complex mechanism of action, and many of the same receptors have been implicated in the effects of neuroactive steroids and ethanol. The goal of this study was to determine whether actions of neuroactive steroids and ethanol at multiple receptors result in similar discriminative stimulus effects. Rats discriminated 5.6 mg/kg of pregnanolone while responding under a fixed-ratio 20 schedule of food presentation. Pregnanolone, flunitrazepam and pentobarbital produced >80% pregnanolone-lever responding. In contrast, neither morphine nor the negative GABA(A) modulator beta-CCE substituted for pregnanolone up to doses that markedly decreased response rates. Ethanol substituted only in some rats; in other rats, ethanol produced <20% pregnanolone-lever responding up to rate-decreasing doses. Thus, substitution of positive GABA(A) modulators, and not morphine or beta-CCE, for pregnanolone in all rats suggests that positive modulation of GABA(A) receptors is important in the discriminative stimulus effects of pregnanolone. Although pregnanolone might have actions at other receptors, in addition to actions at GABA(A) receptors, substitution of ethanol for pregnanolone only in some rats suggests that the mechanisms of action of pregnanolone and ethanol overlap, but are not identical. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/18328551/Overlapping_but_not_identical_discriminative_stimulus_effects_of_the_neuroactive_steroid_pregnanolone_and_ethanol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(08)00052-X DB - PRIME DP - Unbound Medicine ER -