Neuropharmacological characterization of local ibogaine effects on dopamine release

Local perfusion with ibogaine (10(-6)M-10(-3)M) via microdialysis probes in the nucleus accumbens or striatum of rats produced a biphasic dose-response effect on extracellular dopamine levels. Lower doses (10(-6)-M-10(-4)M) produced a decrease while higher doses (5 x 10(-4)M-10(-3)M) produced an increase in dopamine levels. Dihydroxyphenylacetic acid (DOPAC) levels were not effected. Naloxone (10(-6)M) and norbinaltorphimine (10(-6)M-10(-5)M) did not affect dopamine levels, but when co-administered with ibogaine (10(-4)M) blocked the decrease in dopamine levels produced by ibogaine. Ibogaine (10(-3)M) stimulation of dopamine levels in the striatum was calcium independent and not blocked by tetrodotoxin (10(-5)M). Pretreatment with cocaine (15 mg/kg), reserpine (5 mg/kg) or alpha-methyl-para-tyrosine (250 mg/kg) given intraperitoneally significantly reduced ibogaine (10(-3)M) stimulation of striatal dopamine levels. In striatal synaptosomes, both ibogaine and harmaline (10(-7)-10(-4)M) produced dose-dependent inhibition of [H-3]-dopamine uptake. These findings suggest that ibogaine has both inhibitory and stimulatory effects on dopamine release at the level of the nerve terminal. It is suggested that the inhibitory effect is mediated by kappa opiate receptors while the stimulatory effect is mediated by interaction with the dopamine uptake transporter.