Escalation of methamphetamine self-administration in rats: a dose-effect function
Escalation of methamphetamine self-administration in rats: a dose-effect function
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DOI：
10.1007/s00213-006-0353-z
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Pulvirenti, L
中科院分区：
文献类型：
--
作者：
Kitamura, O;Wee, S;Pulvirenti, L
理论基础：在自我给药的可卡因和海洛因的大鼠身上，已经证明了从稳定的药物摄入量到逐渐增加的药物摄入量。目的：探讨甲基苯丙胺长期自我给药情况及不同训练剂量甲基苯丙胺对21天甲基苯丙胺摄入量变化的影响。方法：对两组大鼠进行每日1-h的甲基苯丙胺训练[0.033 mg/次(Inf)；约0.066 mg/kg/次(Inf)]。甲基苯丙胺在一组[长通道(LGA)]增加到6h或在另一组[短通道(SHA)]维持在1h。同样的过程在暴露于不同训练剂量的甲基苯丙胺(0.05、0.1和0.2 mg/kg/inf)的大鼠中重复。结果：在LGA大鼠中，不同剂量的甲基苯丙胺总摄入量和第一小时摄入量均显著高于沙鼠。在第二项研究中，在所有剂量下，LGA动物的摄入量增加到每6小时8-9毫克/公斤，其中最快的增加发生在3-5天，甲基苯丙胺剂量为0.1毫克/公斤/平方英寸。结论：多次服用甲基苯丙胺可引起药物摄入量的增加。升级的速度取决于剂量。最终，剂量-反应研究中的所有剂量都会导致扩展访问组在6小时的疗程中自我给药相同数量的总药物。结果表明，升级的速度依赖于剂量，在21天内有一个摄入量上限。
Rationale: The transition from stable to escalated drug intake has been demonstrated in rats self-administrating cocaine and heroin using a single dose of drug. Objectives: To investigate the prolonged exposure to methamphetamine self-administration and the effect of various training doses of methamphetamine on the changes of methamphetamine intake over a 21-day period. Methods: Two groups of rats were trained in 1-h daily sessions of methamphetamine self-administration [0.033 mg/infusion (inf); approximately 0.066 mg/kg/inf]. Methamphetamine access was increased to 6 h in one group [Long Access (LgA)] or maintained at 1 h in another [Short Access (ShA)]. The same procedure was repeated in rats exposed to different training doses of methamphetamine (0.05, 0.1, and 0.2 mg/kg/inf). Results: In LgA rats, total and first hour intake of methamphetamine significantly increased compared to ShA rats at various methamphetamine doses. LgA animals, at all doses in the second study, escalated intake to 8-9 mg/kg per 6-h session, with the most rapid escalation occurring at 3-5 days at a methamphetamine dose of 0.1 mg/kg/inf. Conclusions: The escalation of drug intake observed with extended access is produced at multiple doses of methamphetamine. The rapidity of escalation depends on the dose. Ultimately, all doses in the dose-response study engendered self-administration of the same amount of total drug in a 6-h session in the extended-access group. Results suggest that the rapidity of escalation is dependent on dose and has an upper limit of intake over a period of 21 days.