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AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antagonist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was recorded in the nucleus accumbens (Nac) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing patte in the Nac neurons during cumulative doses. High dose of THPB- 18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on Nac firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the D1 selective antagonist SCH23390. The tested Nac neurons were effectively inhibited by iontophoretically applied THPB-18 in 90% of 6-OHDA-lesioned rats, while THPB-18 caused variable effects on the firing of Nac neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine,THPB-18 also possesses the "D1 agonistic-D2 antagonistic" dual action on the VTA-Nac DA system.