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 nicotine treatments on the secretion of immunoreactive beta-endorphin (IR-beta-EP) and cell viability of cultured hypothalamic neurons. Also, we determined the secretory response of IR-beta-EP following withdrawal from a long-term nicotine treatment. Fetal hypothalamic cells were dissociated and maintained in cultures for 9 days and were treated with various doses of nicotine (1, 6, 12 and 18 microM) for 6 h (acute treatment) or treated with nicotine at 12 h intervals for 96 h (chronic treatment). Determination of IR-beta-EP concentrations in the media revealed that 6-18 microM doses of nicotine increased IR-beta-EP secretion from 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 microM) 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-secreting neurons and, 3) beta-EP neurons in primary culture show withdrawal response to nicotine.