SEX-DIFFERENCES IN IBOGAINE ANTAGONISM OF MORPHINE-INDUCED LOCOMOTOR-ACTIVITY AND IN IBOGAINE BRAIN LEVELS AND METABOLISM

The present study demonstrates that the putative antiaddictive agent i bogaine produces more robust behavioral effects in female than in male rats and that these behavioral differences correlate with higher leve ls of ibogaine in the brain and plasma of female rats. There were no d ifferences in basal locomotor activity between the sexes, and the resp onse of rats to ibogaine differed between the sexes even in the absenc e of morphine. Five h after receiving ibogaine (40 mg/kg, IF), antagon ism of morphine-induced locomotor activity was evident in female but n ot in male rats. Either 19 h af ter administration of ibogaine (10-60 mg/kg, IF), or one h after administration of noribogaine (5-40 mg/kg, IF), a suspected metabolite, antagonism of morphine was significantly greater in female than in male rats. Brain and plasma levels of ibogai ne (1 h) and noribogaine (5 h), measured by gas chromatography-mass sp ectrometry, were greater in females as compared with males receiving t he same dose of ibogaine. Levels of both ibogaine and noribogaine were substantially lower at 19 h than at earlier times after ibogaine admi nistration, contrary to a previous study in humans. For both sexes, su bcutaneous administration of ibogaine (40 mg/kg, IF, 19 h) produced gr eater antagonism of morphine-induced locomotor activity than did a com parable intraperitoneal injection, consistent with previous studies fr om this laboratory demonstrating that the former route of administrati on produces higher levels of ibogaine in the brain. These data show th at there are sex differences in the effects of ibogaine and that this may be due to decreased bioavailability of ibogaine in males as compar ed to females. (C) 1997 Elsevier Science Inc.