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對甲基苯丙胺（METH）誘導的大鼠條件位置偏愛（CPP）效應(yīng)的影響。方法 通過CPP實驗，以METH為陽性藥，觀察Y-QA31（12.5、25、50 mg/kg，ip）自身致CPP潛力；通過CPP實驗建立大鼠METH精神依賴模型，觀察Y-QA31（6.25、12.5、25、50 mg/kg，ip）預處理是否干預模型的形成、表達、復吸。結(jié)果 0.5 mg/kg METH可誘導大鼠產(chǎn)生明顯的CPP；Y-QA31自身不能誘導大鼠形成CPP；伴隨給予Y-QA31不能阻止METH誘導大鼠CPP的形成；表達期單次給予Y-QA31能劑量依賴性降低METH誘導的大鼠CPP的表達；Y-QA31可抑制METH誘導大鼠CPP的復吸。結(jié)論 Y-QA31能抑制METH的獎賞效應(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.

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