Tags

Type your tag names separated by a space and hit enter

Effects of pregnanolone alone and in combination with other positive GABAA modulators on complex behavior in rats.
Psychopharmacology (Berl). 2004 Apr; 173(1-2):195-202.P

Abstract

RATIONALE

Although positive modulators of gamma-aminobutyric acid(A) (GABA(A)) receptors generally produce similar behavioral effects, regardless of which modulatory site on the GABA(A) receptor complex mediates these effects, some differences have been observed between the effects of neuroactive steroids and those of other positive GABA(A) modulators.

OBJECTIVE

The current study was designed to compare the behavioral effects of a neuroactive steroid to those of other positive GABA(A) modulators.

METHODS

Rats responded under a multiple schedule of repeated acquisition and performance of response chains, with responding maintained under a second-order fixed-ratio 2 schedule of food presentation.

RESULTS

Pregnanolone, flunitrazepam, pentobarbital and ketamine, an antagonist at NMDA receptors, dose-dependently decreased response rates and increased the percentage of errors in both components of the multiple schedule. Although the rate-decreasing and error-increasing effects of pregnanolone, pentobarbital and ketamine were quantitatively similar to each other, flunitrazepam was less effective in decreasing response rates and more effective in increasing errors than the other three drugs. A dose of 3.2 mg/kg pregnanolone potentiated the effects of flunitrazepam and pentobarbital, producing 2- to 3-fold shifts to the left in the dose-effect curves. In contrast, pregnanolone did not alter the ketamine dose-effect curves.

CONCLUSIONS

The disruptive effects of the neuroactive steroid pregnanolone are qualitatively similar to those of other positive GABA(A) modulators as well as ketamine; however, the potentiation of the effects of flunitrazepam and pentobarbital, and not ketamine, emphasizes the importance of GABA(A) receptors in the behavioral effects of pregnanolone.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112-1393, USA. lgerak@lsuhsc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14740146

Citation

Gerak, Lisa R., et al. "Effects of Pregnanolone Alone and in Combination With Other Positive GABAA Modulators On Complex Behavior in Rats." Psychopharmacology, vol. 173, no. 1-2, 2004, pp. 195-202.
Gerak LR, Stevenson MW, Winsauer PJ, et al. Effects of pregnanolone alone and in combination with other positive GABAA modulators on complex behavior in rats. Psychopharmacology (Berl). 2004;173(1-2):195-202.
Gerak, L. R., Stevenson, M. W., Winsauer, P. J., & Moerschbaecher, J. M. (2004). Effects of pregnanolone alone and in combination with other positive GABAA modulators on complex behavior in rats. Psychopharmacology, 173(1-2), 195-202.
Gerak LR, et al. Effects of Pregnanolone Alone and in Combination With Other Positive GABAA Modulators On Complex Behavior in Rats. Psychopharmacology (Berl). 2004;173(1-2):195-202. PubMed PMID: 14740146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of pregnanolone alone and in combination with other positive GABAA modulators on complex behavior in rats. AU - Gerak,Lisa R, AU - Stevenson,Michael W, AU - Winsauer,Peter J, AU - Moerschbaecher,Joseph M, Y1 - 2004/01/22/ PY - 2003/07/30/received PY - 2003/11/01/accepted PY - 2004/1/24/pubmed PY - 2004/8/7/medline PY - 2004/1/24/entrez SP - 195 EP - 202 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 173 IS - 1-2 N2 - RATIONALE: Although positive modulators of gamma-aminobutyric acid(A) (GABA(A)) receptors generally produce similar behavioral effects, regardless of which modulatory site on the GABA(A) receptor complex mediates these effects, some differences have been observed between the effects of neuroactive steroids and those of other positive GABA(A) modulators. OBJECTIVE: The current study was designed to compare the behavioral effects of a neuroactive steroid to those of other positive GABA(A) modulators. METHODS: Rats responded under a multiple schedule of repeated acquisition and performance of response chains, with responding maintained under a second-order fixed-ratio 2 schedule of food presentation. RESULTS: Pregnanolone, flunitrazepam, pentobarbital and ketamine, an antagonist at NMDA receptors, dose-dependently decreased response rates and increased the percentage of errors in both components of the multiple schedule. Although the rate-decreasing and error-increasing effects of pregnanolone, pentobarbital and ketamine were quantitatively similar to each other, flunitrazepam was less effective in decreasing response rates and more effective in increasing errors than the other three drugs. A dose of 3.2 mg/kg pregnanolone potentiated the effects of flunitrazepam and pentobarbital, producing 2- to 3-fold shifts to the left in the dose-effect curves. In contrast, pregnanolone did not alter the ketamine dose-effect curves. CONCLUSIONS: The disruptive effects of the neuroactive steroid pregnanolone are qualitatively similar to those of other positive GABA(A) modulators as well as ketamine; however, the potentiation of the effects of flunitrazepam and pentobarbital, and not ketamine, emphasizes the importance of GABA(A) receptors in the behavioral effects of pregnanolone. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/14740146/Effects_of_pregnanolone_alone_and_in_combination_with_other_positive_GABAA_modulators_on_complex_behavior_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-003-1717-2 DB - PRIME DP - Unbound Medicine ER -