LACK OF CATECHOLAMINE INVOLVEMENT IN THE INCREASED LUTEINIZING-HORMONE RELEASE DUE TO BLOCKADE OF KAPPA-OPIOID RECEPTORS IN THE MEDIAL BASAL HYPOTHALAMUS DURING MIDPREGNANCY IN THE RAT

Blockade of kappa-opioid receptors in the medial basal hypothalamus (MBH) with nor-binaltorphimine (nor-BNI) stimulates luteinizing hormone (LH) release during midpregnancy in the rat [48]. The objective of this study was to determine whether norepinephrine (NE) or dopamine (DA) mediates the LH response to blockade of MBH kappa-opioid receptors on days 13-17 of pregnancy in the rat. Two experiments were conducted. In the first, push-pull perfusion in conjunction with HPLC was used to monitor in vivo NE release in the MBH occurring in response to (a) artificial CSF followed by CSF containing nor-BNI (40 mu g/h), (b) desipramine (DMI, a NE reuptake blocker, 10 mu M) in CSF followed by DMI, and (c) DMI followed by DMI + nor-BNI. Blood samples were taken at 12 min intervals concurrent with push-pull perfusate samples. Plasma LH levels were determined by RIA. Nor-BNI significantly increased LH release compared to CSF alone, but perfusate NE was undetectable in either perfusion period. However, perfusion with CSF containing 100 mM K+ in these rats markedly increased perfusate NE levels, indicating noradrenergic nerve terminals were present at the perfusion sites in the MBH. Addition of DMI to the CSF significantly increased perfusate NE levels, but produced no change in LH release. Nor-BNI + DMI perfusion increased LH secretion similar to nor-BNI alone, but produced no additional increase in MBH perfusate NE levels compared to perfusion with DMI alone. In the second experiment, push-pull perfusion in the MBH with nor-BNI was done in rats pretreated either with the NE synthesis inhibitor FLA-63 (25 mg/kg, s.c.), the alpha-adrenergic receptor blocker phentolamine (5 mg/kg, i.v.), the DA receptor antagonist d-butaclamol (1 mg/kg, s.c.), or vehicle. None of these drug treatments affected the increased LH release occurring during MBH perfusion with nor-BNI. The present results demonstrate that neither NE nor DA mediates the increased LH release occurring in response to blockade of kappa-opioid receptors in the MBH during midpregnancy in the rat.