MONOSODIUM GLUTAMATE-INDUCED REDUCTIONS IN HYPOTHALAMIC BETA-ENDORPHIN CONTENT RESULT IN MU-OPIOID RECEPTOR UP-REGULATION IN THE MEDIAL PREOPTIC AREA

Estradiol valerate (EV) treatment in the rat induces a lesion of the hypothalamic arcuate nucleus, resulting in significant decreases in hypothalamic beta-endorphin. In addition, the EV treatment causes a selective increase in mu-opioid binding in the medial preoptic area (MPOA). Since beta-endorphin neurons located in the arcuate nucleus project extensively to the MPOA, we have hypothesized that the EV-induced loss of these afferents induces a compensatory upregulation of mu-opioid receptors in opioid target neurons. In order to test this hypothesis, we have utilized monosodium glutamate (MSG) treated animals as a model of beta-endorphin cell loss and hence of beta-endorphin deafferentation of the MPOA. Neonatal MSG treatment has been shown to result in the destruction of 80-90% of arcuate neurons accompanied by pronounced decreases in beta-endorphin concentrations in both arcuate nucleus and MPOA. Mu-opioid binding sites were radioautographically labeled in sections from the MPOA of sham- and MSG-injected animals using the methionine enkephalin analogue I-125-FK 33-824 and quantitated by computer-assisted densitometry. The remainder of the hypothalamus of these same animals was utilized for the determination of the beta-endorphin concentration. The hypothalami of rats treated with MSG exhibited 62% (p < 0.01) less beta-endorphin than saline-injected controls. In addition, the mean mu-opioid-binding densities in the MPOA were 24% (p < 0.05) above controls in the MSG-treated group. Linear regression analysis of hypothalamic beta-endorphin concentrations and mu-opioid-binding densities within the same animals yielded an inverse proportional relationship with a coefficient of correlation of -0.85 and a goodness of fit of 0.7. These results substantiate the hypothesis that EV-induced destruction of beta-endorphin neurons in the arcuate nucleus may result in chronic mu-opioid receptor upregulation in the MPOA and further suggest that beta-endorphin may regulate mu-opioid receptor density in this area.