THE SECRETORY RESPONSE OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS TO ACUTE AND CHRONIC NICOTINE TREATMENTS AND FOLLOWING NICOTINE WITHDRAWAL

In the present study, we determined the effect of acute and chronic ni cotine treatments on the secretion of immunoreactive beta-endorphin (I R-beta-EP) and cell viability of cultured hypothalamic neurons. Also, we determined the secretory response of IR-beta-EP following withdrawa l from a longterm nicotine treatment. Fetal hypothalamic cells were di ssociated and maintained in cultures for 9 days and were treated with various doses of nicotine (1, 6, 12 and 18 mu M) for 6 h (acute treatm ent) or treated with nicotine at 12 h intervals for 96 h (chronic trea tment). Determination of IR-beta-EP concentrations in the media reveal ed that 6-18 mu M doses of nicotine increased LR-beta-EP secretion fro m these cultures for a period of 24 h; after this period, the cultured cells did not respond to these doses of nicotine. The desensitization of beta-EP neurons 24 h after treatment with nicotine did not appear to be related to the loss of viable cells. Determination of withdrawal response after 72 h of constant nicotine (6 mu M) treatments revealed that the hypothalamic neurons secrete elevated amounts of IR-beta-EP for a period of 72 h after nicotine withdrawal. These results suggest that: 1) acute treatment with nicotine stimulates hypothalamic IR-beta -EP release; 2) chronic nicotine treatment desensitizes beta-EP-secret ing neurons and, 3) beta-EP neurons in primary culture show withdrawal response to nicotine. (C) 1997 Elsevier Science Inc.