Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: interactions with D-amphetamine.
Brain research – November 19, 1993
Source: PubMed
Summary
Local administration of ibogaine at 10 microM decreased extracellular DOPAC levels, mirroring the long-lasting effects seen with systemic doses (40 mg/kg) that altered dopamine levels for up to 20 hours. High concentrations (200-400 microM) produced acute effects, reducing dopamine and increasing its metabolites within 3 hours. Additionally, ibogaine enhanced the impact of D-amphetamine on dopamine levels, suggesting a complex interaction between these substances. These findings raise questions about ibogaine's potential anti-addictive properties and its mechanisms in the brain's dopaminergic regions.
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.