Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR 97239, USA.
Genes Brain Behav. 2011 Aug;10(6):625-36. doi: 10.1111/j.1601-183X.2011.00700.x. Epub 2011 May 31.
Amphetamines have rewarding and aversive effects. Relative sensitivity to these effects may be a better predictor of vulnerability to addiction than sensitivity to one of these effects alone. We tested this hypothesis in a dose-response study in a second replicate set of mouse lines selectively bred for high vs. low methamphetamine (MA) drinking (MADR). Replicate 2 high (MAHDR-2) and low (MALDR-2) MA drinking mice were bred based on MA consumption in a two-bottle choice procedure and examined for novel tastant drinking. Sensitivities to the rewarding and aversive effects of several doses of MA (0.5, 2 and 4 mg/kg) were measured using a place conditioning procedure. After conditioning, mice were tested in a drug-free and then drug-present state for time spent in the saline- and MA-paired contexts. Similar to the first set of MADR lines, by the end of selection, MAHDR-2 mice consumed about 6 mg MA/kg/18 h, compared to nearly no MA in MALDR-2 mice, but had similar taste preference ratios. MAHDR-2 mice exhibited place preference in both the drug-free and drug-present tests, and no significant place aversion. In contrast, MALDR-2 mice exhibited no place preference or aversion during the drug-free test, but robust place aversion in the drug-present test. These data extend our preliminary findings from the first set of MADR lines and support the hypothesis that the combination of greater sensitivity to the rewarding effects of MA and insensitivity to the aversive effects of MA is genetically associated with heightened risk for MA consumption.
苯丙胺具有奖赏和厌恶的作用。对这些作用的相对敏感性可能比对这些作用中单一作用的敏感性更能预测对成瘾的易感性。我们在一组选择性繁殖的用于高与低 methamphetamine（MA）饮用（MADR）的小鼠系的剂量反应研究中测试了这一假设。在基于 MA 消耗的双瓶选择程序中繁殖了第二组重复的高（MAHDR-2）和低（MALDR-2）MA 饮用小鼠，并检查了新的味觉饮料。使用位置条件反射程序测量了几种剂量的 MA（0.5、2 和 4 mg/kg）的奖赏和厌恶作用的敏感性。在条件作用后，在无药物和有药物的状态下测试小鼠，以测量其在盐水和 MA 配对环境中的时间。与第一组 MADR 系相似，在选择结束时，MAHDR-2 小鼠消耗约 6 mg MA/kg/18 h，而 MALDR-2 小鼠几乎不消耗 MA，但具有相似的味觉偏好比。MAHDR-2 小鼠在无药物和有药物的测试中均表现出位置偏好，而没有明显的位置厌恶。相比之下，MALDR-2 小鼠在无药物测试中没有表现出位置偏好或厌恶，但在有药物的测试中表现出强烈的位置厌恶。这些数据扩展了我们从第一组 MADR 系获得的初步发现，并支持了这样一种假设，即对 MA 的奖赏作用的敏感性增加和对 MA 的厌恶作用的不敏感性的组合与 MA 消耗的风险增加在遗传上相关。
