Elsevier

Neuroscience

Volume 65, Issue 3, April 1995, Pages 775-783
Neuroscience

Release of β-endorphin immunoreactivity from brain by activation of a hypothalamicN-methyl-d-aspartate receptor

https://doi.org/10.1016/0306-4522(94)00528-DGet rights and content

Abstract

Lateral ventricle-cisterna magna perfusion in the halothane-anesthetized rat was used as a model to study β-endorphin release in the brain. Microinjection ofN-methyl-d-aspartate into the arcuate nucleus of the hypothalamus released β-endorphin immunoreactivity into perfusate and the release was blocked by systemic pretreatment with theN-methyl-d-aspartate antagonist dizocilpine (MK-801).N-methyl-d-aspartate microinjections did not increase β-endorphin immunoreactivity in plasma, and pretreatment with dexamethasone did not prevent release of β-endorphin immunoreactivity into perfusate, emphasizing that the released β-endorphin immunoreactivity did not come from plasma. The non-N-methyl-d-aspartate glutamate receptor agonist α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide did not release β-endorphin immunoreactivity. High-performance liquid chromatography characterization of perfusates collected afterN-methyl-d-aspartate microinjection showed that a major part, but not all, of the β-endorphin immunoreactivity co-eluted with authentic β-endorphin1–31.

Microinjection ofN-methyl-d-aspartate provoked an algogenic response in the anesthetized rat, and inhibited the motor and cardiovascular responses to tail immersion in 52.5°C water. This block was reversed by pretreatment with MK-801, but not naloxone. Injection of α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide elicited the same behavioral response and blocked the nociceptive tail-dip reaction, but did not release β-endorphin immunoreactivity. This dissociation suggests that the β-endorphin immunoreactivity releasing effect ofN-methyl-d-aspartate injection into the arcuate nucleus illustrates a specific regulatory activation ofN-methyl-d-aspartate glutamate receptors, and is not a result of a non-specific activation of the arcuate nucleus.

In thisin vivo, anesthetized preparation including three tail immersions into hot water, β-endorphin can be released into a ventriculo-cisternal perfusate, and the response to tail immersion in hot water blocked, by acute activation ofN-methyl-d-aspartate receptors in the arcuate nucleus. The present data do not, however, provide evidence for a role of the released β-endorphin in nociceptive regulation.

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