Accumulating evidence indicates that a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors(AMPARs) are involved in the relapse to abused drugs.However, the role of AMPARs containing the Glu R2 subunit in op...Accumulating evidence indicates that a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors(AMPARs) are involved in the relapse to abused drugs.However, the role of AMPARs containing the Glu R2 subunit in opiate addiction is still unclear. Glu R2-3Y,an interfering peptide, prevents the endocytosis of AMPARs containing the Glu R2 subunit. In this study, we explored the effect of intravenous injection of Glu R2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference(m CPP) in rats. We found that infusion of Glu R2-3Y(1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of m CPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of m CPP. Injection of Glu R2-3Y(1.5 nmol/g) after m CPP extinction blocked the morphine-induced reinstatement of m CPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.展开更多
利用心得安阻断β-肾上腺素受体(β-受体),从而干扰药物成瘾患者对药物环境线索记忆的某些环节(如再巩固等),进而降低或抑制其对成瘾药物的渴求,已成为未来治疗复吸的潜在途径。但目前,心得安对吗啡相关环境线索记忆的获得及提取的影响...利用心得安阻断β-肾上腺素受体(β-受体),从而干扰药物成瘾患者对药物环境线索记忆的某些环节(如再巩固等),进而降低或抑制其对成瘾药物的渴求,已成为未来治疗复吸的潜在途径。但目前,心得安对吗啡相关环境线索记忆的获得及提取的影响尚不清楚。因此,该实验检测了心得安对小鼠吗啡诱导的条件化位置偏爱(conditioned place preference,CPP)环境线索记忆的获得和提取的影响。该研究首次发现在吗啡CPP记忆的获得期,心得安不影响CPP的表达和消退,提示β-受体不参与吗啡诱导CPP学习记忆的获得;而在吗啡CPP记忆的提取期,心得安可延缓CPP的消退,提示β-受体与吗啡诱导CPP学习记忆的提取相关。该结果表明,药物成瘾过程与β-受体相关,为成瘾等精神疾病的治疗提供了新的理论依据。展开更多
基金supported by grants from the National Natural Science Foundation of China(81171043,31400880)the Key Laboratory of Mental Health,Institute of Psychology,Chinese Academy of Sciences,China(KLMH2014ZG02)
文摘Accumulating evidence indicates that a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors(AMPARs) are involved in the relapse to abused drugs.However, the role of AMPARs containing the Glu R2 subunit in opiate addiction is still unclear. Glu R2-3Y,an interfering peptide, prevents the endocytosis of AMPARs containing the Glu R2 subunit. In this study, we explored the effect of intravenous injection of Glu R2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference(m CPP) in rats. We found that infusion of Glu R2-3Y(1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of m CPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of m CPP. Injection of Glu R2-3Y(1.5 nmol/g) after m CPP extinction blocked the morphine-induced reinstatement of m CPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.
文摘利用心得安阻断β-肾上腺素受体(β-受体),从而干扰药物成瘾患者对药物环境线索记忆的某些环节(如再巩固等),进而降低或抑制其对成瘾药物的渴求,已成为未来治疗复吸的潜在途径。但目前,心得安对吗啡相关环境线索记忆的获得及提取的影响尚不清楚。因此,该实验检测了心得安对小鼠吗啡诱导的条件化位置偏爱(conditioned place preference,CPP)环境线索记忆的获得和提取的影响。该研究首次发现在吗啡CPP记忆的获得期,心得安不影响CPP的表达和消退,提示β-受体不参与吗啡诱导CPP学习记忆的获得;而在吗啡CPP记忆的提取期,心得安可延缓CPP的消退,提示β-受体与吗啡诱导CPP学习记忆的提取相关。该结果表明,药物成瘾过程与β-受体相关,为成瘾等精神疾病的治疗提供了新的理论依据。