Rapid down-regulation of GABA-A receptors after pretreatment of mice with progesterone.
The effect of a single administration of a high dose of progesterone on brain [3H]muscimol binding, was examined in mice using quantitative autoradiography. It was found that progesterone given at the dose of 150 mg/kg ip (the ED85 dose established previously in the model of picrotoxin seizures, Członkowska et al., Pharmacol. Biochem. Behav., 2000, 67, 345-353), significantly decreased the specific binding of [3H]muscimol to the nucleus caudatus and nucleus accumbens, as early as 1 h after injection. A similar tendency, close to the statistically significant level, was also present in the dentate gyrus of the hippocampus (p = 0.07). It is suggested that a high dose of progesterone and ensuing excessive stimulation of GABAA receptors by its metabolites, neurosteroids, could bring about rapid changes in the GABAA receptor number and/or affinity.
Członkowska
A I
AI
Department of Experimental and Clinical Pharmacology, Medical University, Warszawa, Poland.
Krzaścik
P
P
Sienkiewicz-Jaros
H
H
Siemiqtkowski
M
M
Szyndler
J
J
Maciejak
P
P
Bidziński
A
A
Plaźnik
A
A
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D018755:GABA Agonists / Q000378:metabolism; D008297:Male; D051379:Mice; D009118:Muscimol / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D018755:GABA Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D011374:Progesterone