Ibogaine antagonizes cocaine-induced locomotor stimulation in mice.

In mice, ibogaine reduced the increased movement caused by cocaine, both shortly after injection and 24 hours later, indicating the effect was not just short-term depression. When ibogaine was given after three days of daily cocaine, movement was still lower on days 5 and 9 without further ibogaine. Ibogaine did not affect amphetamine-induced movement. It transiently increased dopamine turnover, then decreased it in the striatum and frontal cortex after 24 hours. Ibogaine did not alter cocaine binding to its striatal site in vitro and had weak affinity there. The results suggest ibogaine may selectively change the dopamine system, reducing cocaine responsiveness for at least a week.

Study at a glance

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.