Neural Loci Involved in Naloxone-Induced Luteinizing Hormone Release: Effects of a Norepinephrine Synthesis Inhibitor*

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Abstract
Subcutaneous injections of opiate receptor antagonist, naloxone, stimulated LH release in ovariectomized estradiol benzoate (day 0, 1000 h) and progesterone (day 2, 1000 h) treated rats, and this response was probably mediated by noradrenergic (NE) neurons (Kalra, S. P., Simpkins, J. M.: Endocrinology 109: 776, 1981). We have now attempted to identify the central loci of opiate-NE interaction concerned with LH release in these steroid-pretreated rats. Placement of implants, containing naloxone crystals on day 2 at 1200 h unilaterally at sites previously known to influence LH release and/or innervated by NE neurons, such as locus coeruleus, medial raphae nucleus, amygdaloid complex, medial lemniscus, septal-diagonal band of Broca, or ventro-dorsomedial hypothalamus failed to stimulate LH release. In contrast, similar naloxone-implants or injections of naloxone solution (50 μg/2 μl) in the medial preoptic area (MPOA) or the median eminence-arcuate region (MEARC) promptly stimulated LH release. Naloxone-implants at these sites induced LH increments within 10 min, and significantly higher levels were apparent until 120 min. Further, prior stimulation of opiate receptors with morphine sulphate administration (40 mg/kg) blocked the stimulatory effects of naloxone implants in the MPOA or ME-ARC on LH release. In addition, when NE levels in the preoptic area and medial basal hypothalamus were suppressed by pretreatment with diethyldithiocarbomate (500 mg/kg), naloxone implants at these sites failed to augment LH release. These studies show that 1) opiate receptors concerned with LH release may be localized in the MPOA and ME-ARC regions, 2) normal levels of NE in axons and terminals in the MPOA and ME-ARC may be essential in order to stimulate LH release with naloxone, and 3) since the naloxone-responsive sites and LHRH neurons are coextensive in the MPOA and ME-ARC, a functional axo-axonic interaction between the opioid peptide and NE neurons may occur in the close vicinity of LHRH neurons. (Endocrinology109: 1805, 1981)