Ibogaine reduced cocaine-induced increases in dopamine release in the nucleus accumbens and amplified cocaine-induced decreases in serotonin release in male rats. It also diminished cocaine-stimulated ambulation and central ambulation, behaviors that had habituated over time in the test chamber. Rearing and fine movements, which did not habituate, were not affected by ibogaine. Ibogaine alone did not significantly alter dopamine release over two hours but did increase serotonin release and acted as a weak psychostimulant. The findings highlight a modulatory role for serotonin in ibogaine-cocaine interactions and show ibogaine's efficacy when cocaine responses are reduced by environmental habituation.
In rats, ibogaine applied directly to the nucleus accumbens or striatum via microdialysis had a biphasic effect on extracellular dopamine: lower doses (10⁻⁶ M–10⁻⁴ M) decreased dopamine levels, while higher doses (5×10⁻⁴ M–10⁻³ M) increased them. The dopamine metabolite DOPAC was unaffected. Co-administration with naloxone or norbinaltorphimine blocked the dopamine decrease, suggesting involvement of kappa opioid receptors. The stimulatory effect at high doses was calcium-independent, not blocked by tetrodotoxin, but reduced by cocaine, reserpine, or alpha-methyl-para-tyrosine pretreatment. In striatal synaptosomes, ibogaine and harmaline inhibited dopamine uptake dose-dependently, indicating the stimulatory effect involves the dopamine transporter.