RIVASTIGMINE AS A TREATMENT FOR METHAMPHETAMINE DEPENDENCE

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 摘要 我们最近完成了一项双盲安慰剂对照人体实验室研究，证明低剂量乙酰胆碱酯酶（AChE）抑制剂卡巴拉汀治疗可减少甲基苯丙胺（MA）诱导的渴求（见初步研究，图2）。这一发现与临床前报告一致，该报告表明AChE抑制剂多奈哌齐在暴露于非偶然剂量的MA后减少了大鼠的MA寻求行为（Hiranita等人，2006）。为了扩展我们的临床结果，我们提出了一项为期3年的人体实验室研究，以评价较高剂量的rivastigmine对MA诱导的渴求和MA自我给药的影响。 我们最近完成的工作表明，3 mg rivastigmine在实验室中减弱了MA诱导的渴求。考虑到更高剂量的这种药物对烟碱乙酰胆碱（ACh）受体产生更大的抑制作用（用于治疗阿尔茨海默病），可以合理地预测6毫克和12毫克将对渴望和其他强化措施产生更明显的影响。这项人体实验室研究是评价rivastigmine作为MA依赖潜在治疗的关键下一步。 我们建议通过在入院前筛选潜在参与者，仅纳入表现出MA诱导的渴望的参与者（基于初步研究的标准，图5）。选择表现出MA诱导的渴求的受试者将有助于评估rivastigmine对渴求的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT We recently completed a double-blind placebo-controlled human laboratory study demonstrating that treatment with a low dose of the acetylcholinesterase (AChE) inhibitor rivastigmine reduced methamphetamine (MA)-induced craving (see Preliminary Studies, Fig. 2). This finding is consistent with the preclinical report indicating that the AChE inhibitor donepezil reduced MA-seeking behavior in rats following exposure to a non-contingent dose of MA (Hiranita et al. 2006). To extend our clinical findings, we propose a 3-year human laboratory study to evaluate effects of higher doses of rivastigmine on MA-induced craving and on self-administration of MA. Our recently completed work indicates that 3mg rivastigmine attenuated MA-induced craving in the laboratory. Given that higher dosages of this produce greater inhibition of nicotinic acetylcholine (ACh) receptors (in the treatment of Alzheimers disease), it is reasonable to predict that 6mg and 12mg will have more pronounced effects on craving and other measures of reinforcement. This human laboratory study is a critical next step in the evaluation of rivastigmine as a potential treatment for MA dependence. We propose to include only participants exhibiting MA-induced craving by screening potential participants prior to admission (criterion based upon Preliminary Studies, Fig. 5). Selection of participants demonstrating MA-induced craving will facilitate assessment of effects of rivastigmine on craving.