Acute central stimulation of luteinizing hormone by parenterally administered N-methyl-D,L-aspartic acid in the male rat.

N-methyl-D,L-aspartic acid (NMA), a potent neuroexcitatory and neurotoxic glutamic acid analogue, acutely elevated serum luteinizing hormone (LH) in male rats when given subcutaneously in doses below those that cause morphologically detectable hypothalamic neurotoxicity. NMA treatment in doses known to be subtoxic by morphological criteria fails to induce any permanent neuroendocrine dysfunction as assessed by several physiological parameters, including NMA responsiveness after multiple consecutive dosees spaced at 24 h intervals, subsequent basal LH levels and subsequent postcastration LH elevations. Like naloxone, NMA elevates serum LH by reversibly stimulating a central labile pool. Neither has a direct stimulatory effect on the pituitary in vitro. Treatment with either attenuates naloxone-induced LH stimulation 2 h, but not 14 days, later while pituitary responsiveness to LHRH in vivo remains unaltered. Neither NMA nor naloxone is dependent upon testosterone for its LH stimulatory action and both increase serum LH through physiological mechanisms responsive to testosterone inhibition. It is concluded that subtoxic LH stimulating doses of NMA provide a useful tool in discerning neurotransmitter systems involved in central control of the hypothalamic-pituitary-gonadal axis.