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Vasoactive Intestinal Peptide and Corticotropin‐Releasing Hormone Increase β‐Endorphin Release and Proopiomelanocortin Messenger RNA Levels in Primary Cultures of Hypothalamic Cells: Effects of Acute and Chronic Ethanol Treatment
Author(s) -
Poplawski Michael M.,
Boyadjieva Nadka,
Sarkar Dipak K.
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000158834.11252.2e
Subject(s) - vasoactive intestinal peptide , proopiomelanocortin , medicine , endocrinology , hypothalamus , neuropeptide , receptor , messenger rna , corticotropin releasing hormone , hormone , peptide hormone , substance p , biology , chemistry , gene , biochemistry
Background: β‐Endorphin (β‐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 β‐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 β‐EP neurons in primary cultures of mediobasal hypothalamic cells. The effects of receptor antagonists on VIP‐ and CRH‐induced β‐EP release was determined. Furthermore, the authors studied the effects of acute and chronic treatment with ethanol on the response of β‐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 β‐EP neurons responded concentration dependently to VIP and CRH treatments by increasing both β‐EP release and proopiomelanocortin mRNA expression. Simultaneous treatment with a nonspecific receptor antagonist reduced the ability of CRH or VIP to induce β‐EP release from mediobasal hypothalamic cells. Acute treatment with ethanol increased β‐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 β‐EP release from hypothalamic cells in primary cultures and that the stimulatory and adaptive responses of β‐EP neurons to ethanol may involve alteration in the responsiveness of β‐EP–secreting neurons to CRH and VIP.