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. 1991 Jun;103(2):1580–1584. doi: 10.1111/j.1476-5381.1991.tb09830.x

Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat.

P Westerling 1, S Lindgren 1, B Meyerson 1
PMCID: PMC1908350  PMID: 1653076

Abstract

1. Slices of rat cuneate nucleus were used to study whether or not gonadal steroids influence the gamma-aminobutyric acid (GABA) system in vivo. Females in different stages of the oestrous cycle as well as steroid-treated (oestrogen, progesterone or both) ovariectomized animals were used. 2. Functional changes in the GABAA receptors were assayed using the effects of potentiators (benzodiazepine, barbiturate) and antagonists (picrotoxin) on the muscimol control dose-response curves. 3. The potentiating effect of the benzodiazepine, flurazepam was unchanged during the oestrous cycle, and the hormone treatments did not alter this effect. 4. During oestrus, an increase was seen in the potentiating effect of the barbiturate (pentobarbitone). This suggests a synergistic effect between barbiturates and gonadal steroids. Progesterone treatment also increased the effect of pentobarbitone. 5. The antagonistic action of picrotoxin was unaffected during the oestrous cycle. However, progesterone (or progesterone and oestrogen) treatment reduced the potency of picrotoxin. 6. This study supports the idea that endogenous steroids (presumably progesterone) affect the GABAA receptors during the oestrous cycle by a mechanism associated with the barbiturate site of the GABAA receptor complex.

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Selected References

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  1. Braestrup C., Nielsen M., Olsen C. E. Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2288–2292. doi: 10.1073/pnas.77.4.2288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bäckström T. Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scand. 1976 Oct;54(4):321–347. doi: 10.1111/j.1600-0404.1976.tb04363.x. [DOI] [PubMed] [Google Scholar]
  3. Cottrell G. A., Lambert J. J., Peters J. A. Modulation of GABAA receptor activity by alphaxalone. Br J Pharmacol. 1987 Mar;90(3):491–500. doi: 10.1111/j.1476-5381.1987.tb11198.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gee K. W., Bolger M. B., Brinton R. E., Coirini H., McEwen B. S. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action. J Pharmacol Exp Ther. 1988 Aug;246(2):803–812. [PubMed] [Google Scholar]
  5. Guidotti A., Forchetti C. M., Corda M. G., Konkel D., Bennett C. D., Costa E. Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3531–3535. doi: 10.1073/pnas.80.11.3531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harrison N. L., Simmonds M. A. Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 1984 Dec 10;323(2):287–292. doi: 10.1016/0006-8993(84)90299-3. [DOI] [PubMed] [Google Scholar]
  7. Harrison N. L., Simmonds M. A. Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro. Br J Pharmacol. 1983 Oct;80(2):387–394. doi: 10.1111/j.1476-5381.1983.tb10045.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Landgren S., Aasly J., Bäckström T., Dubrovsky B., Danielsson E. The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex. Acta Physiol Scand. 1987 Sep;131(1):33–42. doi: 10.1111/j.1748-1716.1987.tb08202.x. [DOI] [PubMed] [Google Scholar]
  9. Lindgren S., Simmonds M. A. Adaptation of the GABAA-receptor complex in rat brain during chronic elevation of GABA by ethanolamine O-sulphate. Br J Pharmacol. 1987 Jul;91(3):617–625. doi: 10.1111/j.1476-5381.1987.tb11255.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Majewska M. D., Bisserbe J. C., Eskay R. L. Glucocorticoids are modulators of GABAA receptors in brain. Brain Res. 1985 Jul 22;339(1):178–182. doi: 10.1016/0006-8993(85)90641-9. [DOI] [PubMed] [Google Scholar]
  11. Majewska M. D., Ford-Rice F., Falkay G. Pregnancy-induced alterations of GABAA receptor sensitivity in maternal brain: an antecedent of post-partum 'blues'? Brain Res. 1989 Mar 20;482(2):397–401. doi: 10.1016/0006-8993(89)91208-0. [DOI] [PubMed] [Google Scholar]
  12. Majewska M. D., Harrison N. L., Schwartz R. D., Barker J. L., Paul S. M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 1986 May 23;232(4753):1004–1007. doi: 10.1126/science.2422758. [DOI] [PubMed] [Google Scholar]
  13. Majewska M. D. Steroids and brain activity. Essential dialogue between body and mind. Biochem Pharmacol. 1987 Nov 15;36(22):3781–3788. doi: 10.1016/0006-2952(87)90437-0. [DOI] [PubMed] [Google Scholar]
  14. Meyerson B. J. Relationship between the anesthetic and gestagenic action and estrous behavior-inducing activity of different progestins. Endocrinology. 1967 Aug;81(2):369–374. doi: 10.1210/endo-81-2-369. [DOI] [PubMed] [Google Scholar]
  15. Norberg L., Wahlström G., Bäckström T. The anaesthetic potency of 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one determined with an intravenous EEG-threshold method in male rats. Pharmacol Toxicol. 1987 Jul;61(1):42–47. doi: 10.1111/j.1600-0773.1987.tb01770.x. [DOI] [PubMed] [Google Scholar]
  16. Olsen R. W. Drug interactions at the GABA receptor-ionophore complex. Annu Rev Pharmacol Toxicol. 1982;22:245–277. doi: 10.1146/annurev.pa.22.040182.001333. [DOI] [PubMed] [Google Scholar]
  17. Pickles H. G., Simmonds M. A. Antagonism by penicillin of gamma-aminobutyric acid depolarizations at presynaptic sites in rat olfactory cortex and cuneate nucleus in vitro. Neuropharmacology. 1980 Jan;19(1):35–38. doi: 10.1016/0028-3908(80)90163-x. [DOI] [PubMed] [Google Scholar]
  18. Schmidt R. F. Presynaptic inhibition in the vertebrate central nervous system. Ergeb Physiol. 1971;63:20–101. doi: 10.1007/BFb0047741. [DOI] [PubMed] [Google Scholar]
  19. Simmonds M. A. Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to gamma-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxin. Br J Pharmacol. 1981 Jul;73(3):739–747. doi: 10.1111/j.1476-5381.1981.tb16810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Simmonds M. A. Presynaptic actions of gamma-aminobutyric acid and some antagonists in a slice preparation of cuneate nucleus. Br J Pharmacol. 1978 Jul;63(3):495–502. doi: 10.1111/j.1476-5381.1978.tb07803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Simmonds M. A., Turner J. P. Potentiators of responses to activation of gamma-aminobutyric acid (GABAA) receptors. Neuropharmacology. 1987 Jul;26(7B):923–930. doi: 10.1016/0028-3908(87)90071-2. [DOI] [PubMed] [Google Scholar]
  22. Turner J. P., Simmonds M. A. Modulation of the GABAA receptor complex by steroids in slices of rat cuneate nucleus. Br J Pharmacol. 1989 Feb;96(2):409–417. doi: 10.1111/j.1476-5381.1989.tb11832.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Twyman R. E., Rogers C. J., Macdonald R. L. Pentobarbital and picrotoxin have reciprocal actions on single GABAA receptor channels. Neurosci Lett. 1989 Jan 2;96(1):89–95. doi: 10.1016/0304-3940(89)90248-6. [DOI] [PubMed] [Google Scholar]

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