The N-methyl-d-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat

Abstract

The physiological role of activated hypothalamic N-methyl-D-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0.1-0.2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0.2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0.2, or one injection of 0.5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 x 0.2 mg/kg) or complete (2 x 0.2 and 1 x 0.5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats and ovulated.(ABSTRACT TRUNCATED AT 250 WORDS)