Dopamine transporter-related effects of modafinil in rhesus monkeys.
Dopamine transporter-related effects of modafinil in rhesus monkeys.
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DOI：
10.1007/s00213-010-1839-2
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发表时间：
2010-06
影响因子：
3.4
通讯作者：
Howell, Leonard L.
中科院分区：
文献类型：
--
作者：
Andersen, Monica L.;Kessler, Eileen;Murnane, Kevin S.;McClung, Jessica C.;Tufik, Sergio;Howell, Leonard L.
莫达非尼目前用于治疗白天嗜睡。本研究的目的是探讨莫达非尼对多巴胺转运蛋白（DAT）相关的恒河猴（Macaca mulatta）行为和体内神经化学的影响。评估莫达非尼（3.0-10 mg/kg，静脉注射）对运动活动、可卡因维持行为的恢复、尾状核中的细胞外多巴胺水平以及背侧纹状体中 DAT 占据的影响。八名受试者配备了安装在项圈上的活动监测器来评估睡眠活动周期，在注射生理盐水或莫达非尼（3.0-10 mg/kg）之前进行 4 天的基线记录。莫达非尼（3.0-10 mg/kg）和可卡因（0.3 mg/kg）对恢复先前在静脉注射二级方案下维持的行为的影响。可卡因递送在另一组受试者中进行测试（n = 6）。最后，在受试者内设计（n=4）中，分别使用微透析和正电子发射断层扫描来表征莫达非尼（3.0-10 mg/kg）对细胞外多巴胺水平和体内 DAT 占据的影响。莫达非尼显着增加夜间运动活动并恢复可卡因维持的行为，但不影响白天运动活动。莫达非尼显着增加纹状体细胞外多巴胺水平，其剂量导致 DAT 占有率达到 64.4%（壳核）和 60.2%（尾状核）。莫达非尼的行为和体内多巴胺能作用与低效 DAT 抑制剂的特性一致，可能表明高剂量滥用的可能性。
Modafinil is currently used as a treatment for daytime sleepiness. The objectives of this study were to explore the dopamine transporter (DAT)-related effects of modafinil on behavior and in vivo neurochemistry in rhesus monkeys (Macaca mulatta). The effects of modafinil (3.0–10 mg/kg, i.v.) were evaluated on locomotor activity, reinstatement of cocaine-maintained behavior, extracellular dopamine levels in the caudate nucleus, and DAT occupancy in the dorsal striatum. Eight subjects were fitted with a collar-mounted activity monitor to evaluate sleep-activity cycles, with 4 days of baseline recording preceding an injection of saline or modafinil (3.0–10 mg/kg). The effects of modafinil (3.0–10 mg/kg) and cocaine (0.3 mg/kg) on reinstatement of behavior that was previously maintained under a second-order schedule of i.v. cocaine delivery were tested in a separate group of subjects (n=6). Finally, the effects of modafinil (3.0–10 mg/kg) on extracellular dopamine levels and DAT occupancy in vivo were characterized using microdialysis and positron emission tomography, respectively, in a within-subjects design (n=4). Modafinil significantly increased nighttime locomotor activity and reinstated cocaine-maintained behavior but did not affect daytime locomotor activity. Modafinil significantly increased striatal extracellular dopamine levels at a dose that resulted in DAT occupancy of 64.4% (putamen) and 60.2% (caudate). The behavioral and in vivo dopaminergic effects of modafinil are consistent with the profile of a low potency DAT inhibitor and may indicate potential for abuse at high doses.
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DOI：
10.1124/jpet.106.106583
发表时间：
2006-11-01
影响因子：
3.5
作者：
Madras, Bertha K.;Xie, Zhihua;Fischman, Alan J.
通讯作者：
Fischman, Alan J.
影响因子：
2.4
作者：
Mann, TM;Williams, KE;Scott, EAM
通讯作者：
Scott, EAM
影响因子：
3.4
作者：
Deroche-Gamonet, V;Darnaudéry, M;Piazza, PV
通讯作者：
Piazza, PV
影响因子：
3.4
作者：
Czoty, PW;Justice, JB;Howell, LL
通讯作者：
Howell, LL
影响因子：
4.2
作者：
Anderson, Ann L.;Reid, Malcolm S.;Li, Shou-Hua;Holmes, Tyson;Shemanski, Lynn;Slee, April;Smith, Edwina V.;Kahn, Roberta;Chiang, Nora;Vocci, Frank;Ciraulo, Domenic;Dackis, Charles;Roache, John D.;Salloum, Ihsan M.;Somoza, Eugene;Urschel, Harold C., III;Elkashef, Ahmed M.
通讯作者：
Elkashef, Ahmed M.