Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: interactions with D-amphetamine.

Ibogaine, given systemically, alters dopamine and its metabolites in brain reward regions. When applied directly to the striatum and nucleus accumbens, high concentrations (200-400 µM) mimicked the acute effects of systemic ibogaine, lowering dopamine and raising metabolite levels, while a low concentration (10 µM) reproduced the persistent effect of lowering DOPAC. This suggests ibogaine acts directly on dopaminergic nerve terminals and that long-lasting effects may stem from persisting low ibogaine levels. Locally applied ibogaine also enhanced amphetamine's effect on dopamine, and systemic ibogaine pretreatment enhanced locally applied amphetamine's effect, indicating a pharmacodynamic mechanism contributes to their interaction. The relevance to ibogaine's anti-addictive claims remains unclear.

Study at a glance

Abstract

Systemic administration of ibogaine (40 mg/kg, i.p.) has been reported to induce both acute (1-3 h) and persistent (19-20 h) changes in extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum. In the present study, local administration of ibogaine to the striatum and nucleus accumbens produced effects that mimicked both the acute and persistent effects of systemic administration: perfusion with high concentrations (200 and 400 microM) of ibogaine mimicked the acute effects (decreased extracellular dopamine levels and increased extracellular metabolite levels) whereas perfusion with a low concentration (10 microM) of ibogaine mimicked the persistent effects (decreased extracellular levels of DOPAC). These results indicate that ibogaine acts directly in brain regions containing dopaminergic nerve terminals and that long-lasting effects of systemically administered ibogaine might be mediated by persisting low levels of ibogaine. Locally administered ibogaine (10 microM) was also found to enhance the effects of systemically administered D-amphetamine (1.25 mg/kg, i.p.) on extracellular dopamine levels, and conversely, systemically administered ibogaine (40 mg/kg, i.p.; 19 h pretreatment) enhanced the effects of locally administered D-amphetamine (1-10 microM). These results indicate that, in addition to a metabolic mechanism implicated previously, a pharmacodynamic mechanism contributes to the interaction between ibogaine and D-amphetamine. The relevance of such mechanisms to claims regarding ibogaine's anti-addictive properties is unclear.