The role of norepinephrine in mediating luteinizing hormone release in response to blockade of kappa-opioid receptors in the medial preoptic area.

Our previous study [32] indicated that blockade of kappa-opioid receptors with nor-binaltorphimine (nor-BNI) in the medial preoptic area (MPOA) produced two different LH responses during midpregnancy in the rat: an increase in basal pulsatile LH secretion, followed in many cases by a larger and/or sustained increase in LH release. In the present study, two experiments were conducted to examine the role of norepinephrine (NE) in mediating these different LH responses. In experiment 1, the effects of NE synthesis inhibition with FLA-63 on nor-BNI induced LH secretion were examined. In 5 of 9 vehicle pretreated rats, nor-BNI perfusion in the MPOA produced only an increase in basal pulsatile LH secretion. In the remaining 4 animals blockade of MPOA kappa-receptors produced not only an increase in basal LH secretion, but also a large/sustained release of LH. Pretreatment with FLA-63 had no effect on the nor-BNI induced increase in basal pulsatile LH secretion, but completely prevented the occurrence of the large/sustained release of LH. The objective of experiment 2 was to determine whether any change in NE release occurred at the site of nor-BNI perfusion in rats showing this large/sustained increase in plasma LH levels, by measuring in vivo NE release at that site. No significant change in perfusate NE levels was observed during perfusion of the MPOA with nor-BNI alone or in combination with desipramine, a NE reuptake blocker, in rats that showed this type of LH response. These results demonstrate that while NE does not mediate the increase in basal pulsatile LH release produced by nor-BNI perfusion in the MPOA, it is essential for the large/sustained elevation in LH secretion seen in response to blockade of kappa-opioid receptors at this site. This latter type of LH secretory response is not, however, associated with an increase in NE release directly at the site of kappa-opioid receptor blockade in the MPOA in pregnant rats.