Estradiol benzoate decreases nigral GABAergic activity in male rats.
Repeated doses of estradiol benzoate (10 micrograms/kg, s.c., once a day for 2, 5 or 8 days) to male rats decreased gamma-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity in substantia nigra (SN) but failed to change these parameters in hippocampus, cerebral cortex, cerebellum, lateral septum and olfactory tubercle. In the caudate nucleus, estradiol benzoate decreased GABA concentration but did not modify GAD activity. A decrease in nigral GABA concentration and GAD activity was also observed 24 and 48 but not 3 h after a single injection of estradiol benzoate. These data are consistent with results on GAD activity reported by McGinnis et al. in ovariectomized rats. Kinetic analysis of nigral GAD activity revealed that repeated estradiol benzoate injection reduced the Vmax without affecting the Km of GAD. Estradiol benzoate also reduced the rate of nigral GABA accumulation resulting from local infusion of gabaculine, suggesting that the steroid decreases GABA turnover in male rat SN. Hypophysectomy decreased GABA content and GAD activity in SN and GABA content in striatum. Administration of estradiol benzoate for 8 days to hypophysectomized rats failed to decrease further these parameters. Taken together, these data suggest that estradiol benzoate decreases SN GABAergic activity and that the integrity of the pituitary gland is required for this effect.
Nicoletti
F
F
Meek
J L
JL
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D018756:GABA Antagonists; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D007016:Hypophysectomy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D003509:Cyclohexanecarboxylic Acids; D018756:GABA Antagonists; C012987:gabaculine; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase