SUPPRESSION OF SPLENIC NATURAL-KILLER-CELL ACTIVITY IN A MOUSE MODEL FOR BINGE DRINKING .2. ROLE OF THE NEUROENDOCRINE SYSTEM

Ethanol (EtOH) suppresses natural killer (NK) cell activity in the spl een in a binge drinking model in mice. Direct effects of EtOH and its metabolites are not the major cause of this suppression. In this study , the role of catecholamines, glucocorticoids and opioids in EtOH-indu ced suppression of NK cell activity in mice was evaluated. In addition , the role of GABA-A receptors was examined. The catecholamine antagon ists phentolamine, nadolol and propranolol (delivered by a timed-relea se pellet) respectively exacerbated, partially blocked and had no effe ct on EtOH-induced suppression of NK cell activity. Chemical sympathec tomy significantly reduced the suppression of NK cell activity by EtOH . The glucocorticoid antagonist RU 486 (mifepristone) did not affect E tOH-induced suppression of NK cell activity, and exogenous corticoster one only marginally suppressed NK cell activity. The opioid antagonist naltrexone (delivered by a timed-release pellet) did not block suppre ssion of NK cell activity by EtOH. Thus glucocorticoids and opioids ar e not the major causes of EtOH-induced suppression of NK cell activity , and catecholamines seem only partially responsible for this effect. Involvement of GABA-A receptors was suggested by the ability of Ro15-4 513 to decrease EtOH-induced NK suppression. Other agents were less ef fective, which suggested a possible role for the diazepam-insensitive GABA-A sites that are recognized by Ro15-4513. The failure of diazepam to suppress NK activity also suggests that increased chloride flux th rough diazepam-sensitive GABA-A receptors (which is caused by EtOH as well as diazepam) does not mediate NK suppression in this model.