Ibogaine antagonizes cocaine-induced locomotor stimulation in mice.
H Sershen, A Hashim, L Harsing, A Lajtha
Life sciences January 1, 1992 DOI: 10.1016/0024-3205(92)90344-o
Summary
Ibogaine significantly reduces cocaine-induced locomotor activity in C57BL/6 mice. When given 40 mg/kg two hours before a 25 mg/kg cocaine injection, ibogaine diminished stimulation not only immediately but also after a second injection 24 hours later. Daily cocaine administration for three days followed by ibogaine treatment still showed reduced activity on day four, with effects lasting up to nine days. Interestingly, ibogaine did not impact locomotor responses to amphetamine, suggesting a selective alteration in the dopaminergic system’s response to cocaine.
Abstract
Ibogaine (40 mg/kg i.p.), when given 2 hours before an acute injection of cocaine (25 mg/kg s.c.) to C57BL/6 mice, reduced the cocaine-induced locomotor stimulation. Such stimulation was also reduced in the ibogaine-treated mice when a second injection of cocaine was given 24 hr later. Thus, the reduction in locomotor activity was not just the short-term depression of locomotor activity seen after ibogaine administration. When mice were given a daily injection of cocaine for 3 days and ibogaine was given after the cocaine injection on day 3, and again on day 4, cocaine-induced locomotor activity was reduced three hours later on day 4. On days 5 and 9 of the cocaine administration, with no further ibogaine treatment ambulatory counts were still lower in the ibogaine-pretreated mice. Locomotor stimulation induced by amphetamine (10 mg/kg) was not affected by ibogaine. An acute injection of ibogaine resulted in a transient increase in turnover of dopamine, as indicated by the increase in the ratio of metabolites of the dopamine to dopamine, followed by a decrease in the metabolites in striatum and frontal cortex 24 hr later. In vivo treatment with ibogaine did not affect the binding of [3H]WIN 35,248 to the cocaine binding site in striatal tissue measured in vitro. In addition, ibogaine added in vitro had a weak affinity to the WIN 35,248 binding site (IC50 for cocaine = 120 nM and for ibogaine = 1,500 nM). The results suggest that ibogaine may have induced a selective change in the dopaminergic system that results in a decrease in responsiveness to cocaine that persisted for at least 1 week.