Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine-induced locomotor activity in rats.

Ibogaine, a compound proposed for treating addiction to opiates and stimulants, produces both immediate and lasting changes in brain dopamine levels. One hour after a single injection, dopamine decreased by 50% while its metabolite HVA increased by 37–100% in the striatum, nucleus accumbens, and prefrontal cortex. Nineteen hours later, another metabolite, DOPAC, was reduced in the nucleus accumbens and striatum, and striatal DOPAC remained low after a week. No significant neurochemical changes were present after one month. Ibogaine pretreatment also reduced the stimulatory effect of morphine on movement when morphine was given 19 hours or a week later, but not after a month. These findings suggest ibogaine's effects on dopamine systems coincide with a sustained dampening of morphine-induced motor activity.

Study at a glance

Abstract

Ibogaine, an indolalkylamine, proposed for use in treating opiate and stimulant addiction, has been shown to modulate the dopaminergic system acutely and one day later. In the present study we sought to systematically determine the effects of ibogaine on the levels of dopamine (DA) and the dopamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in tissue at several time points, between 1 h and 1 month post-injection. One hour after ibogaine-administration (40 mg/kg i.p.) a 50% decrease in DA along with a 37-100% increase in HVA were observed in all 3 brain regions studied: striatum, nucleus accumbens and prefrontal cortex. Nineteen hours after ibogaine-administration a decrease in DOPAC was seen in the nucleus accumbens and in the striatum. A week after administration of ibogaine striatal DOPAC levels were still reduced. A month after ibogaine injection there were no significant neurochemical changes in any region. We also investigated the effects of ibogaine pretreatment on morphine-induced locomotor activity, which is thought to depend on DA release. Using photocell activity cages we found that ibogaine pretreatment decreased the stimulatory motor effects induced by a wide range of morphine doses (0.5-20 mg/kg, i.p.) administered 19 h later; a similar effect was observed when morphine (5 mg/kg) was administered a week after ibogaine pretreatment. No significant changes in morphine-induced locomotion were seen a month after ibogaine pretreatment. The present findings indicate that ibogaine produces both acute and delayed effects on the tissue content of DA and its metabolites, and these changes coincide with a sustained depression of morphine-induced locomotor activity.