Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine.
Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine.
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DOI：
10.1111/adb.12003
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发表时间：
2014-05
影响因子：
3.4
通讯作者：
Phillips TJ
中科院分区：
文献类型：
--
作者：
Eastwood EC;Phillips TJ
很少有调查的遗传因素和相关的机制，影响风险的发展甲基苯丙胺（MA）的依赖。在两瓶选择MA饮用（MADR）程序中表现出高（MAHDR）或低（MALDR）水平MA摄入的选择性繁殖小鼠品系为此目的提供了遗传工具。这些线被用来确定阿片类药物的敏感性和MA的摄入量是否是遗传相关的，因为阿片类药物介导的途径影响MA的一些效果。.采用两种急性热试验（热板和甩尾）和一种慢性疼痛试验（硫酸镁腹部收缩）检查对μ-阿片受体（MOP-r）激动剂芬太尼（0.05、0.1、0.2、0.4 mg/kg）镇痛作用的敏感性。芬太尼（0.05，0.1，0.2，0.4 mg/kg）和吗啡（10，20，30 mg/kg）的运动刺激反应也进行了检查。此外，在产生所选品系的F2群体的祖株（C57 BL/6 J（B6）、DBA/2 J（D2））中测量MADR。MADR系对芬太尼镇痛作用的敏感性没有差异;然而，MALDR小鼠对芬太尼和吗啡的运动激活比MAHDR小鼠更大。D2小鼠比B6小鼠消耗更多的MA。MA消耗和吗啡激活的品系差异概括了B6和D2品系在这两个性状上的差异，但没有之前发现的阿片类镇痛反应的品系差异。这些结果支持MA消费和阿片类药物的刺激作用的敏感性之间的负遗传相关性，并建议参与MOP-r调节系统在MA摄入量。
There has been little investigation of genetic factors and associated mechanisms that influence risk for development of methamphetamine (MA) dependence. Selectively bred mouse lines that exhibit high (MAHDR) or low (MALDR) levels of MA intake in a two-bottle choice MA drinking (MADR) procedure provide a genetic tool for this purpose. These lines were used to determine whether opioid sensitivity and MA intake are genetically associated, since opioid mediated pathways influence some effects of MA. . Sensitivity to the analgesic effects of the μ-opioid receptor (MOP-r) agonist fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) was examined using two acute thermal tests (hot plate and tail flick) and one chronic pain test (magnesium sulfate abdominal constriction). Locomotor stimulant responses to fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) and morphine (10, 20, 30 mg/kg) were also examined. In addition, MADR was measured in the progenitor strains (C57BL/6J (B6), DBA/2J (D2)) of the F2 population from which the selected lines were generated. The MADR lines did not differ in sensitivity to the analgesic effects of fentanyl; however, MALDR mice exhibited greater locomotor activation than MAHDR mice to both fentanyl and morphine. D2 mice consumed more MA than B6 mice. The line differences for MA consumption and morphine activation recapitulated B6 and D2 strain differences for these two traits, but not strain differences previously found for opioid analgesic responses. These results support a negative genetic correlation between MA consumption and sensitivity to the stimulant effects of opioids and suggest the involvement of MOP-r regulated systems in MA intake.
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DOI：
10.1124/jpet.107.119560
发表时间：
2007-10-01
影响因子：
3.5
作者：
Kalvass, J. Cory;Olson, Emily R.;Pollack, Gary M.
通讯作者：
Pollack, Gary M.
影响因子：
2.5
作者：
Bergeson, SE;Helms, ML;Belknap, JK
通讯作者：
Belknap, JK
影响因子：
3.5
作者：
Doyle, Glenn A.;Sheng, X. Rebecca;Berrettini, Wade H.
通讯作者：
Berrettini, Wade H.
影响因子：
3.8
作者：
Chiu, CT;Ma, TG;Ho, IK
通讯作者：
Ho, IK
影响因子：
7.4
作者：
MOGIL, JS;MAREK, P;LIEBESKIND, JC
通讯作者：
LIEBESKIND, JC