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

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.