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Anxiolytic effects of 3α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor
Open accessAbstract
The effects of intracerebroventricular administration of reduced metabolites of progesterone on locomotor activity and on exploration in the elevated plus-maze were assessed in adult female rats. Allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one; 1.25, 5.0, and 10 micrograms) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one; 2.5, 5.0, and 10 micrograms) elicited anxiolytic effects and, at the highest dose tested, allopregnanolone resulted in sedation. In contrast, the 3 beta-hydroxy-epimer of allopregnanolone was without effect in either behavioral paradigm. The anxiolytic response to pregnanolone was blocked by picrotoxin (0.75 mg/kg, i.p.), a dose that by itself did not affect behavior in the plus-maze. These data suggest that the anxiolytic effect of 3 alpha-hydroxy metabolites of progesterone is mediated by brain GABAA receptors in a stereospecific manner, and are in good agreement with the well-documented in vitro effects of these steroids as potent modulators of the GABAA receptor.
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Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor
Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., & Paul, S. M. (1986) · Science · doi:10.1126/science.2422758 · Cited by 2,225
Turner, D. M., Ransom, R. W., Yang, J. S., & Olsen, R. W. (1989) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24172-6 · Cited by 275
Cited by
Multiple Actions of Steroid Hormones—A Focus on Rapid, Nongenomic Effects
Falkenstein, E., Tillmann, H.-C., Christ, M., Feuring, M., & Wehling, M. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01468-6 · Cited by 991
GABAA receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid
Smith, S. S., Gong, Q. H., Hsu, F.-C., Markowitz, R. S., ffrench-Mullen, J. M. H., & Li, X. (1998) · Nature · doi:10.1038/31948 · Cited by 564
Nongenomic steroid action: controversies, questions, and answers
LÖSEL, R. M., FALKENSTEIN, E., FEURING, M., SCHULTZ, A., TILLMANN, H.-C., ROSSOL-HASEROTH, K., & WEHLING, M. (2003) · Physiological Reviews · doi:10.1152/physrev.00003.2003 · Cited by 561
Neurosteroids: biochemistry and clinical significance
Mellon, S. H., & Griffin, L. D. (2002) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(01)00503-3 · Cited by 538
Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties
Rupprecht, R. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00064-1 · Cited by 427
Metadata
- Authors
- Bitran, D., Hilvers, R. J., & Kellogg, C. K.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1991-10
- Volume
- 561
- Issue
- 1
- Pages
- 157-161
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2012767314
- Cited by
- 457
- References
- 2
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Bitran, D., Hilvers, R. J., & Kellogg, C. K. (1991). Anxiolytic effects of 3α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor. Brain Research. https://doi.org/10.1016/0006-8993(91)90761-j
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