THE ROLE OF CAMP IN ETHANOL-REGULATED BETA-ENDORPHIN RELEASE FROM HYPOTHALAMIC NEURONS

We have previously shown that ethanol acutely stimulates immunoreactiv e beta-endorphin (IR-beta-EP) release from hypothalamic neurons, where as chronic administration of ethanol desensitizes these neurons. In th e study reported herein, the role of the intracellular cAMP system in the ethanol-regulated IR-beta-EP release from hypothalamic cells in pr imary cultures was investigated, Acute treatment with ethanol or with the cAMP analog, dibutyryl cAMP, revealed that hath agents stimulate t he release of IR-beta-EP from the hypothalamic cells. Combined treatme nt of ethanol and the cAMP analog produced a synergistic effect on IR- beta-EP release. Treatment with ethanol and a cAMP-elevating agent, fo rskolin, increased cAMP levels in cultured hypothalamic cells. However , prior exposure to ethanol reduced the cAMP-elevating responses of th ese neurons to ethanol and forskolin. These results indicate that the stimulatory and adaptive responses of IR-beta-EP neurons to ethanol ma y involve the cAMP system.