Vasoactive Intestinal Peptide and Corticotropin-Releasing Hormone Increase beta-Endorphin Release and Proopiomelanocortin Messenger RNA Levels in Primary Cultures of Hypothalamic Cells: Effects of Acute and Chronic Ethanol Treatment.

摘要

BACKGROUND:: beta-Endorphin (beta-EP) neurons are involved in ethanol's action on a variety of brain functions, including positive reinforcement. These neurons are innervated by vasoactive intestinal peptide (VIP)-containing and corticotropin-releasing hormone (CRH)-containing neurons in the hypothalamus. Whether these neuropeptides affect beta-EP neuronal function in the presence or absence of ethanol has not previously been determined. METHODS:: The authors determined the effects of VIP and CRH on gene expression and peptide release from beta-EP neurons in primary cultures of mediobasal hypothalamic cells. The effects of receptor antagonists on VIP- and CRH-induced beta-EP release was determined. Furthermore, the authors studied the effects of acute and chronic treatment with ethanol on the response of beta-EP neurons to VIP and CRH. Real-time reverse-transcription polymerase chain reaction was used for messenger RNA (mRNA) detection, and radioimmunoassay was used for hormone measurements. RESULTS:: We show that beta-EP neurons responded concentration dependently to VIP and CRH treatments by increasing both beta-EP release and proopiomelanocortin mRNA expression. Simultaneous treatment with a nonspecific receptor antagonist reduced the ability of CRH or VIP to induce beta-EP release from mediobasal hypothalamic cells. Acute treatment with ethanol increased beta-EP neuronal gene expression and the secretory response to CRH and VIP. However, previous exposure to chronic ethanol reduced the CRH and VIP responses of these neurons. CONCLUSIONS:: These results indicate that VIP and CRH stimulate beta-EP release from hypothalamic cells in primary cultures and that the stimulatory and adaptive responses of beta-EP neurons to ethanol may involve alteration in the responsiveness of beta-EP-secreting neurons to CRH and VIP.