RELEASE OF BETA-ENDORPHIN IMMUNOREACTIVITY FROM BRAIN BY ACTIVATION OF A HYPOTHALAMIC N-METHYL-D-ASPARTATE RECEPTOR

Lateral ventricle-cisterna magna perfusion in the halothane-anesthetiz ed rat was used as a model to study beta-endorphin release in the brai n. Microinjection of N-methyl-D-aspartate into the arcuate nucleus of the hypothalamus released beta-endorphin immunoreactivity into perfusa te and the release was blocked by systemic pretreatment with the N-met hyl-D-aspartate antagonist dizocilpine (MK-801). N-methyl-D-aspartate microinjections did not increase beta-endorphin immunoreactivity in pl asma, and pretreatment with dexamethasone did not prevent release of b eta-endorphin immunoreactivity into perfusate, emphasizing that the re leased beta-endorphin immunoreactivity did not come from plasma. The n on-N-methyl-D-aspartate glutamate receptor agonist lpha-amino-3-hydrox y-5-methylisoxazole-4-propionic acid hydrobromide did not release beta -endorphin immunoreactivity. High-performance liquid chromatography ch aracterization of perfusates collected after N-methyl-D-aspartate micr oinjection showed that a major part, but not all, of the beta-endorphi n immunoreactivity co-eluted with authentic beta-endorphin(1-31). Micr oinjection of N-methyl-D-aspartate provoked an algogenic response in t he anesthetized rat, and inhibited the motor and cardiovascular respon ses to tail immersion in 52.5 degrees C water. This block was reversed by pretreatment with MK-801, but not naloxone. Injection of lpha-amin o-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide elicited t he same behavioral response and blocked the nociceptive tail-dip react ion, but did not release beta-endorphin immunoreactivity. This dissoci ation suggests that the beta-endorphin immunoreactivity releasing effe ct of N-methyl-D-aspartate injection into the arcuate nucleus illustra tes a specific regulatory activation of N-methyl-D-aspartate-type glut amate receptors, and is not a result of a non-specific activation of t he arcuate nucleus. In this in vivo, anesthetized preparation includin g three tail immersions into hot water, beta-endorphin can be released into a ventriculo-cisternal perfusate, and the response to tail immer sion in hot water blocked, by acute activation of N-methyl-D-aspartate receptors in the arcuate nucleus. The present data do not, however, p rovide evidence for a role of the released beta-endorphin in nocicepti ve regulation.