目的 探討多巴胺D3受體拮抗劑苯并噻唑啉-2-酮-甲酰胺類化合物Y-QA31對(duì)甲基苯丙胺（METH）誘導(dǎo)的大鼠條件位置偏愛(ài)（CPP）效應(yīng)的影響。方法 通過(guò)CPP實(shí)驗(yàn)，以METH為陽(yáng)性藥，觀察Y-QA31（12.5、25、50 mg/kg，ip）自身致CPP潛力；通過(guò)CPP實(shí)驗(yàn)建立大鼠METH精神依賴模型，觀察Y-QA31（6.25、12.5、25、50 mg/kg，ip）預(yù)處理是否干預(yù)模型的形成、表達(dá)、復(fù)吸。結(jié)果 0.5 mg/kg METH可誘導(dǎo)大鼠產(chǎn)生明顯的CPP；Y-QA31自身不能誘導(dǎo)大鼠形成CPP；伴隨給予Y-QA31不能阻止METH誘導(dǎo)大鼠CPP的形成；表達(dá)期單次給予Y-QA31能劑量依賴性降低METH誘導(dǎo)的大鼠CPP的表達(dá)；Y-QA31可抑制METH誘導(dǎo)大鼠CPP的復(fù)吸。結(jié)論 Y-QA31能抑制METH的獎(jiǎng)賞效應(yīng)，在成癮治療中發(fā)揮一定作用。

Objective To study the effect of compound of Benzothiazoline-2-ketone-formamide:Y-QA31 on conditioned place preference (CPP) induced by methamphetamine (METH). Methods The CPP potential of Y-QA31 (12.5, 25 and 50 mg/kg, IP) was observed by the CPP experiment and METH as the positive drug. METH-induced CPP was established in rats. The acquisition, expression and reinstatement of CPP was influenced by Y-QA31 (6.25, 12.5, 25 and 50 mg/kg, ip). The results of each group were compared and analzsed. Results 0.5 mg/kg METH induced cpp; (1) Y-QA31 failed in inducing CPP in rats; (2) repetitive injection of YQA31(daily during the METH conditioning)did not alter the acquisition of METH-induced CPP; (3) a single injection of YQA31 (prior to CPP test) dose-dependently attenuated the expression of METH-induced CPP; (4) a single injection of YQA31 decreased the reinstatement of METH-induced CPP. Conclusion Y-QA31 can inhibit the rewarding effect induced by METH and may play a role in the treatment of METH addiction.

國(guó)家“重大新藥創(chuàng)制”科技重大專項(xiàng)（2017ZX09101-005-007、2016ZX08011007、2017ZX09201008-001-002、ZDYZ2015-2）