NALOXONE INCREASES THE FREQUENCY OF THE ELECTRICAL-ACTIVITY OF LUTEINIZING-HORMONE-RELEASING HORMONE PULSE-GENERATOR IN LONG-TERM OVARIECTOMIZED RATS

Characteristic increases in neuronal activity accompanied by the initiation of each luteinizing hormone (LH) pulse have been successfully recorded in freely moving ovariectomized rats by means of multiunit activity (MUA) recording techniques. In the present study, the effect of the opioid receptor antagonist naloxone on this neuronal activity was examined in rats ovariectomized for 6-10 weeks. Electrodes were chronically implanted into the medial basal hypothalamus (n = 78) or the medial preoptic area (n = 29). During the MUA recording, blood samples were taken through an indwelling atrial cannula at 3- or 6-min intervals to determine the serum LH concentration. Naloxone was administered intravenously for 1 h by either intermittent injection every 6 min (0.05 mg/kg, 10 times) or continuous infusion (0.1, 0.2 and 0.5 mg/kg/h). Explosive rises in the MUA (volleys) associated with the initiation of LH pulse were recorded in 7 animals in which the tips of electrodes were located in the arcuate nucleus-median eminence region. In 5 animals studied, the mean (+/- SE) duration and interval of the MUA volleys were 2.1 +/- 0.1 and 22.1 +/- 0.9 min, respectively. Naloxone given every 6 min significantly increased the duration to 2.6 +/- 0.1 min, and decreased the interval to 9.5 +/- 0.9 min. This naloxone treatment disturbed the clear pulsatility of LH secretion observed in the pretreatment control period. Analysis of the effects of naloxone infused at 3 different doses revealed that the facilitatory effects of naloxone on the duration and frequency of the MUA volleys were dose-dependent. These results suggest that endogenous opioid peptides have tonic inhibitory effects on the LH-releasing hormone pulse generator activity and are profoundly involved in the control of the frequency of pulsatile LH secretion in the ovariectomized rat.