4-PHENYLTETRAHYDROISOQUINOLINE, BUT NOT NOMIFENSINE OR COCAINE, INHIBITS METHAMPHETAMINE-INDUCED DOPAMINE RELEASE

The inhibitory effect of 4-phenyltetrahydroisoquinoline (4-PTIQ) on me thamphetamine-induced dopamine release in the rat nucleus accumbens wa s investigated using a brain microdialysis method. Methamphetamine (10 (-6) M) infusion through a microdialysis probe induced the release of dopamine. Although the uptake inhibitors, cocaine (3 x 10(-6) M) and n omifensine (10(-6) M), failed to block dopamine release, 4-PTIQ (10(-6 ) M) inhibited the dopamine-releasing effect of methamphetamine. 4-PTI Q did not affect the elevation of the extracellular dopamine level ind uced by high concentrations of nomifensine (10(-5) M) and cocaine (3 x 10(-5) M). 4-PTIQ was the weakest inhibitor of [H-3]dopamine uptake b y rat striatal synaptosomes. These results suggest that 4-PTIQ is a se lective antagonist against the dopamine-releasing effect of methamphet amine in the nucleus accumbens.