EFFECTS OF INTRACEREBROVENTRICULAR ADMINISTRATION OF D,L-2-AMINO-5-PHOSPHONOVALERIC ACID, AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, ON LUTEINIZING-HORMONE RELEASE IN OVARIECTOMIZED LAMBS

To determine whether endogenous glutamate and aspartate control LH secretion via N-methyl-D-aspartate (NMDA) receptors in the sheep, we evaluated the effects of the NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) on secretion of LH in ovariectomized lambs. Twelve lambs were ovariectomized and surgically implanted with lateral cerebroventricular cannulae. At the time of the experiment, (38 wk of age) they received intracerebrally 4 injections of either 50 (n = 4), 100 (n = 4), or 200 mug (n = 4) of AP5. Blood samples were collected every 10 min for 8 h with animals receiving AP5 at hours 4, 5, 6, and 7. Patterns of LH during the preinjection period were compared to those during the period encompassing AP5 injections. Mean concentrations of LH were lower during AP5 injections than during the preinjection periods, a response that was not influenced by dose (0.87 +/-0.08 vs. 0.69 +/- .07 ng/ml; p < 0.01). LH pulse amplitude decreased during AP5 treatment relative to the preinjection periods, but this difference was not statistically significant (0.79 +/- 0.11 vs, 0.68 +/- 0.10 ng/ml; p = 0.09). There were no effects of AP5 on LH pulse frequency (1.00 +/- 0.10 vs. 0.83 +/- 0.15 pulses/h for injection and preinjection periods; p > 0.10). A second experiment was done to evaluate a higher dose of AP5. Four animals were chosen to receive 4 injections of 2 mg of AP5 in a design identical to that used in the first experiment. Injections were discontinued after the second (5 h) injection because 3 of the lambs began to salivate excessively and became extremely lethargic. The 2-mg dose of AP5 had no effect on either mean LH (1.04 +/- 0.07 ng/ml; p > 0.20) or LH pulse frequency (1.56 +/- 0.5 pulses/h; p > 0.50), but decreased (p < 0.05) LH pulse amplitude (0.46 +/- 0.06 vs. 0.32 +/- 0.03 ng/ml). In summary, blockade of the NMDA receptor with AP5 did not suppress pulsatile secretion of LH, suggesting that endogenous aspartate or glutamate are not involved in the control of pulsatile LH secretion via the NMDA receptor in the ovariectomized lamb.