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 recept ors with nor-binaltorphimine (nor-BNI) in the medial preoptic area (MP OA) 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 st udy, two experiments were conducted to examine the role of norepinephr ine (NE) in mediating these different LH responses. In experiment 1, t he effects of NE synthesis inhibition with FLA-63 on nor-BNI induced L H 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 th e nor-BNI induced increase in basal pulsatile LH secretion, but comple tely prevented the occurrence of the large/sustained release of LH. Th e 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 wa s observed during perfusion of the MPOA with nor-BNI alone or in combi nation with desipramine, a NE reuptake blocker, in rats that showed th is type of LH response. These results demonstrate that while NE does n ot mediate the increase in basal pulsatile LH release produced by nor- BNI perfusion in the MPOA, it is essential for the large/sustained ele vation in LH secretion seen in response to blockade of kappa-opioid re ceptors at this site. This latter type of LH secretory response is not , however, associated with an increase in NE release directly at the s ite of kappa-opioid receptor blockade in the MPOA in pregnant rats.