Pharmacology, biochemistry, and behavior
January 1, 1994
H Sershen, A Hashim, A Lajtha
75 citations
Male C57BL/6By mice developed a preference for cocaine after forced exposure to it in drinking water. When given a choice, they consumed 71% of their fluid from the cocaine solution. Ibogaine administration reduced cocaine preference to 41% and daily cocaine intake by 38% for at least five days. Cocaine-challenged mice previously exposed to cocaine showed increased locomotor activity and stereotypy, which were reduced after ibogaine treatment. Brain cocaine levels were about 25% higher in ibogaine-treated mice, suggesting ibogaine may alter cocaine pharmacokinetics.
Life sciences
January 1, 1992
H Sershen, A Hashim, L Harsing et al.
65 citations
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.
Life sciences
January 1, 1992
H Sershen, L G Harsing, A Hashim et al.
33 citations
Ibogaine hydrochloride reduced the locomotor stimulation caused by low-to-moderate doses of d-amphetamine in male mice, an effect that lasted two days, but did not block the effect of a high dose. A lower dose of ibogaine was ineffective. Ibogaine decreased striatal dopamine levels by 30%, while d-amphetamine increased them by 26%. In rats, ibogaine pretreatment paradoxically increased d-amphetamine-induced locomotion, indicating species specificity. The findings suggest ibogaine can modulate dopamine-related behavioral effects in a dose- and species-dependent manner.
Brain research bulletin
January 1, 1997
H Sershen, A Hashim, A Lajtha
32 citations
Ibogaine, an indole alkaloid, may help treat drug dependence. Animal studies show it reduces some effects of stimulant drugs, like motor stimulation and self-administration. The mechanism likely involves dopamine, serotonin, NMDA, kappa, and/or sigma receptor sites, based on binding competition studies, though receptor affinity alone does not prove involvement. In vitro perfusion studies help clarify ibogaine's effects on neurotransmitter systems and their functional consequences. This review summarizes evidence for ibogaine's multiple effects, highlighting the potential importance of its action on serotonergic modulation of dopamine release.
Journal of neural transmission. General section
January 1, 1994
L G Harsing, H Sershen, A Lajtha
26 citations
Ibogaine increases the release of dopamine from mouse striatum in a concentration-dependent way, primarily from the cytoplasmic pool rather than from vesicles, and this release is not regulated by presynaptic autoreceptors. The effect is reduced by dopamine uptake inhibitors but not by removing calcium or blocking sodium channels. Ibogaine does not affect dopamine uptake or retention. The dopamine-releasing action may contribute to its hallucinogenic effects observed in African ritual practices.
Brain research bulletin
January 1, 1995
H Sershen, A Hashim, A Lajtha
25 citations
Ibogaine, an indole alkaloid, may help interrupt stimulant drug dependency by affecting dopamine release in the brain's striatum. In mouse striatal tissue, the kappa-opioid agonist U 62066 reduced stimulated dopamine release, but ibogaine pretreatment (40 mg/kg IP given 2 hours prior or 2 x 40 mg/kg with animals killed 18 hours later) eliminated this effect. The 5-HT3 agonist phenylbiguanide had a biphasic effect: at 10(-6) M it reduced release, while at 10(-5) M it increased basal outflow. Ibogaine pretreatment did not alter release with 10(-6) M phenylbiguanide but increased stimulated outflow with 10(-5) M. Cocaine (10(-6) M) increased electrically-evoked dopamine release, and ibogaine did not affect this. Ibogaine's modulation of kappa-opioid and 5-HT3 receptors on dopamine terminals may underlie its antiaddictive properties.
Neurochemical research
November 1, 1994
H Sershen, A Hashim, A Lajtha
23 citations
Ibogaine, given to rats and mice, blocked a serotonin receptor's ability to increase dopamine release in striatal tissue. Two hours after treatment, ibogaine did not alter serotonin or dopamine uptake. The 5HT1B agonist CGS-12066A normally elevated dopamine efflux, but this effect was absent in animals pretreated with ibogaine 2 or 18 hours earlier. Dopamine autoreceptor responses remained unaffected. The lasting interference with serotonergic modulation of dopamine release may help explain ibogaine's anti-addictive properties.
Pharmacology, biochemistry, and behavior
April 1, 1996
H Sershen, A Hashim, A Lajtha
21 citations
Ibogaine, a compound with structural similarity to serotonin, blocks cocaine's effect on serotonin release in mouse striatal tissue, which in turn modulates dopamine release. In mice treated with ibogaine, cocaine no longer increased electrically evoked serotonin efflux, though dopamine efflux remained elevated. A kappa-opioid agonist reduced both dopamine and serotonin release, an effect blocked by ibogaine pretreatment. The kappa-opioid agonist also restored cocaine-induced serotonin release in ibogaine-treated tissue. These findings suggest ibogaine's antiaddictive properties involve blocking cocaine's serotonergic effects and altering kappa-opioid modulation of serotonin transmission.
Brain research bulletin
January 1, 1996
H Sershen, A Hashim, A Lajtha
19 citations
Ibogaine, an indole alkaloid, inhibits NMDA- and sigma-receptor-mediated dopamine release in mouse striatal tissue. In vitro, ibogaine at 1 µM reduced NMDA-evoked dopamine release by 31% and sigma-receptor-evoked release by 48%. Ibogaine alone at 10 µM increased dopamine efflux, while 1 µM had no effect. The elevated basal dopamine release after evoked release in ibogaine-treated tissue suggests ibogaine may remove tonic inhibition by the kappa-opioid system, which normally reduces dopamine release presynaptically and also inhibits NMDA and sigma receptors.