Peripubertal treatment with N-methyl-D-aspartic acid or neonatally with monosodium glutamate accelerates sexual maturation in female rats, an effect reversed by MK-801.
Recent reports from several laboratories have implicated the excitatory neurotransmitter glutamate as a component in the neural regulation of sexual maturation. In the rat we have previously proposed that a hypothalamic opioid restraint mechanism may ultimately be overridden by maturation of an excitatory drive, culminating in first ovulation. We have now investigated whether glutamate may be the excitatory factor. Treatment of immature female rats with single, daily injections of two N-methyl-D-aspartate (NMDA) antagonists--dextrorphan (18 mg/kg) and MK-801 (0.1 mg/kg)--beginning on the 27th postnatal day, significantly delayed the timing of vaginal opening (VO). Interestingly, treated rats reached VO in spite of continued antagonist treatment. The antagonist effect was reversed by preinjection of NMDA, suggesting that endogenous glutamate exerts its effect via an NMDA-subtype glutamate receptor. Injection of NMDA alone (15 mg/kg; once daily) produced a striking synchronization of VO such that all treated rats showed VO over a 24-hour period compared to a normal distribution of several days for control rats. In a model of first ovulation, i.e., rats induced to ovulate by pregnant mare serum, MK-801 (1 mg/kg) arrested treated rats at proestrus. This was readily reversible after discontinuing injections. A lower dose of MK-801 (0.1 mg/kg/day) was ineffective in delaying ovulation. In a second series of experiments we studied the consequences of a neonatal hypothalamic lesion which destroys glutamate-sensitive neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
MacDonald
M C
MC
Department of Physiology and Biophysics, School of Medicine, Dalhousie University, Halifax, Canada.
Wilkinson
M
M
D000818:Animals; D000831:Animals, Newborn; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010060:Ovulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation / Q000187:drug effects*; D012970:Sodium Glutamate / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects
D005971:Glutamates; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D012970:Sodium Glutamate