Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats.
Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats.
复制标题
DOI：
10.1097/fbp.0000000000000340
复制
发表时间：
2018-03
影响因子：
1.6
通讯作者：
Stairs DJ
中科院分区：
文献类型：
--
作者：
Kangiser MM;Dwoskin LP;Zheng G;Crooks PA;Stairs DJ
甲基苯丙胺是一种强有力的精神刺激剂，滥用比率很高。目前，还没有FDA批准的治疗甲基苯丙胺成瘾的药物疗法。理想情况下，药物治疗应该选择性地减少甲基苯丙胺的自我给药，而不会影响对其他增强剂的反应。检验这一点的一种方法是使用多个强化计划，在一个疗程中，药物和食物以交替的成分提供。本研究评价了泡状单胺转运体2(VMAT2)抑制剂GZ-793A和α4β2的部分激动剂和α7烟碱型乙酰胆碱受体(NAChRs)的完全激动剂varenicline在多重强化方案下减少甲基苯丙胺和食物自我给药的能力。雄性SD大鼠自体静脉注射。甲基苯丙胺(0.03 mg/kg/次输注)和食物颗粒在多重增援计划下。GZ-793A或varenicline在多次计划会话之前给药。与生理盐水相比，GZ-793A(5 mg/kg和20 mg/kg)显著减少甲基苯丙胺的摄入量，并且不改变食物维持反应。相比之下，varenicline减少了甲基苯丙胺的摄入量，而不是随着时间的推移。结果提示，VMAT2抑制可能是治疗甲基苯丙胺使用障碍的一个可行的药理靶点。
Methamphetamine is a potent psychostimulant with high abuse rates. Currently, there is no FDA-approved pharmacotherapy for methamphetamine addiction. Ideally, a pharmacotherapy should selectively decrease methamphetamine self-administration without affecting responding for other reinforcers. One way to test this is with the use of a multiple schedule of reinforcement, in which drug and food are available in alternating components within a session. The present study evaluated GZ-793A, a vesicular monoamine transporter-2 (VMAT2) inhibitor, and varenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptors (nAChRs), for their ability to decrease methamphetamine and food self-administration using a multiple schedule of reinforcement. Male Sprague-Dawley rats self-administered i.v. methamphetamine (0.03 mg/kg/infusion) and food pellets under a multiple schedule of reinforcement. GZ-793A or varenicline was administered prior to multiple schedule sessions. GZ-793A (5 and 20 mg/kg) significantly decreased methamphetamine intake compared to saline, and did not alter food-maintained responding. In contrast, varenicline decreased methamphetamine intake less specific across time. The results suggest that VMAT2 inhibition may be a viable pharmacological target for the treatment of methamphetamine use disorders.