NEUROPHARMACOLOGICAL CHARACTERIZATION OF LOCAL IBOGAINE EFFECTS ON DOPAMINE RELEASE

Local perfusion with ibogaine (10(-6)M-10(-3)M) via microdialysis prob es in the nucleus accumbens or striatum of rats produced a biphasic do se-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 ac id (DOPAC) levels were not effected. Naloxone (10(-6)M) and norbinalto rphimine (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 dopami ne levels in the striatum was calcium independent and not blocked by t etrodotoxin (10(-5)M). Pretreatment with cocaine (15 mg/kg), reserpine (5 mg/kg) or alpha-methyl-para-tyrosine (250 mg/kg) given intraperito neally significantly reduced ibogaine (10(-3)M) stimulation of striata l dopamine levels. In striatal synaptosomes, both ibogaine and harmali ne (10(-7)-10(-4)M) produced dose-dependent inhibition of [H-3]-dopami ne uptake. These findings suggest that ibogaine has both inhibitory an d stimulatory effects on dopamine release at the level of the nerve te rminal. It is suggested that the inhibitory effect is mediated by kapp a opiate receptors while the stimulatory effect is mediated by interac tion with the dopamine uptake transporter.