Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes

【Abstract】 AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antago- nist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was re- corded in the nucleus accumbens (NAc) neurons of na?ve 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 pattern 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.4Now in Department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,4Now in Department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,更多还原