Monosodium glutamate-induced reductions in hypothalamic beta-endorphin content result in mu-opioid receptor upregulation 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 125I-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Desjardins
G C
GC
Department of Neurology and Neurosurgery, Montreal Neurological Institute, Canada.
Brawer
J R
JR
Beaudet
A
A
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001345:Autoradiography; D009474:Neurons / Q000187:drug effects; D011301:Preoptic Area / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D012970:Sodium Glutamate / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*; D001615:beta-Endorphin / Q000378:metabolism*
D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; D012970:Sodium Glutamate