Limited responsiveness of LHRH neurons to norepinephrine may account for failure of locus coeruleus or medullary A1 electrical stimulation to increase plasma LH in estrogen-treated ovariectomized rats.

We recently reported that electrical stimulation (ES) of the locus coeruleus (LC) or the medullary A1 noradrenergic cell groups markedly increased LH secretion. However, these amplifying effects occurred only in rats in which preliminary electrochemical stimulation (ECS) of the medial preoptic nucleus (MPN) was performed. In contrast, ES of either LC or A1 alone did not alter basal LH secretion. Possible explanations for this dichotomy in LH response include: (1) LHRH neurons in unanesthetized, estrogen-treated ovariectomized (OVX) rats are relatively unresponsive to NE, (2) the chloral hydrate anesthesia used in our brain stimulation studies elevates the threshold of excitability of LHRH neurons to norepinephrine (NE) and/or pituitary responsiveness to LHRH, (3) preliminary MPN-ECS reduces thresholds of responsiveness of LHRH neurons to NE, and (4) the LHRH secreted after MPN-ECS sensitizes the pituitary gland to the subsequent small amounts of LHRH released following LC- or A1-stimulation. To provide answers to these questions, 3 experiments were performed in estrogen-treated OVX rats into which had been inserted the third ventricle and jugular cannulae. In the first study, the effects of artificial cerebrospinal fluid (ACSF) or ACSF + NE (5, 20, or 45 micrograms) on plasma LH concentrations in unanesthetized, unrestrained rats were examined. The intracerebroventricular (ICV) infusion of 5 micrograms of NE increased plasma LH by 61.3% above basal levels within 10 min whereas 20 or 45 micrograms NE elevated LH values 166.9 and 182.8%, respectively. The next study examined the effects of anesthetic drugs on LH response produced by ICV infusions of 45 micrograms of NE. Regardless of whether rats were anesthetized with ether, chloral hydrate, urethane, Saffan (alphaxolone + alphadolone) or ketamine + acepromazine, peak LH responses to ICV NE were not significantly different from unanesthetized controls. In a second study we observed that ICV NE (45 micrograms) markedly amplified and prolonged the release of LH after MPN-ECS. Moreover, the peak LH responses in these animals were approximately 10 x greater than those obtained in rats which received ICV NE but not MPN-ECS. The third series of studies demonstrated that pituitary responsiveness to LHRH was not an important factor in dictating the LH response obtained after NE ICV infusions. These data suggest that LHRH neurons in estrogen-primed OVX rats are not particularly responsive to NE and that following MPN-ECS, LHRH neuronal responsiveness to this catecholamine markedly increases.