The role of cAMP in ethanol-regulated beta-endorphin release from hypothalamic neurons

We have previously shown that ethanol acutely stimulates immunoreactive beta-endorphin (IR-beta-EP) release from hypothalamic neurons, whereas chronic administration of ethanol desensitizes these neurons. In the study reported herein, the role of the intracellular cAMP system in the ethanol-regulated IR-beta-EP release from hypothalamic cells in primary cultures was investigated. Acute treatment with ethanol or with the cAMP analog, dibutyryl cAMP, revealed that both agents stimulate the release of IR-beta-EP from the hypothalamic cells. Combined treatment of ethanol and the cAMP analog produced a synergistic effect on IR-beta-EP release. Treatment with ethanol and a cAMP-elevating agent, forskolin, increased cAMP levels in cultured hypothalamic cells. However, prior exposure to ethanol reduced the cAMP-elevating responses of these neurons to ethanol and forskolin. These results indicate that the stimulatory and adaptive responses of IR-beta-EP neurons to ethanol may involve the cAMP system.