Division of Neuroscience, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.
Neuropsychopharmacology. 2012 Dec;37(13):2837-45. doi: 10.1038/npp.2012.155. Epub 2012 Sep 5.
Cognitive enhancers that act by increasing glycine transmission might be useful adjuncts to cocaine-cue extinction training to deter relapse. The study investigated the effects of combining treatments of the glycine transporter-1 (GlyT-1) inhibitor, Org24598, with extinction training on the subsequent reacquisition of cocaine self-administration. Squirrel monkeys and rats were trained to self-administer cocaine under a second-order schedule of intravenous drug injection in which responding was maintained by cocaine injections and a cocaine-paired visual stimulus. During three weekly extinction sessions, saline was substituted for cocaine but responding still produced the cocaine-paired stimulus. Subjects were treated with Org24598 or vehicle, either before or after each extinction session. One week later, cocaine injections were restored, and reacquisition of cocaine self-administration was evaluated over 15 sessions. Compared with vehicle, administration of Org24598 (1.0 mg/kg in monkeys; 3.0 or 7.5 mg/kg in rats) before each extinction session significantly inhibited reacquisition of cocaine self-administration in each species. In contrast, administration of Org24598 (1.0 mg/kg in monkeys) following, rather than preceding, each extinction session did not affect reacquisition compared with vehicle. When extinction training was replaced by cocaine self-administration or abstinence control conditions, treatment with the same doses of Org24598 resulted in reacquisition that was significantly more rapid than the reacquisition observed when Org24598 was administered before extinction training sessions. The results support the potential clinical utility of GlyT-1 inhibitor pretreatments combined with cocaine-cue extinction training to inhibit relapse.
通过增加甘氨酸传递而起作用的认知增强剂可能是可卡因线索消除训练的有用辅助手段，以阻止复发。该研究调查了联合使用甘氨酸转运蛋白-1（GlyT-1）抑制剂 Org24598 与消退训练对可卡因自我给药随后重新获得的影响。松鼠猴和大鼠接受训练，根据静脉内药物注射的二阶时间表自我给予可卡因，其中反应由可卡因注射和可卡因配对的视觉刺激维持。在三个每周的消退会议期间，用生理盐水代替可卡因，但反应仍然产生可卡因配对的刺激。用 Org24598 或载体治疗，在每次消退会议之前或之后。一周后，恢复可卡因注射，并在 15 个疗程中评估可卡因自我给药的重新获得。与载体相比，在每次消退会议之前给予 Org24598（猴子 1.0mg/kg；大鼠 3.0 或 7.5mg/kg）可显著抑制两种物种可卡因自我给药的重新获得。相比之下，与载体相比，在每次消退会议之后而不是之前给予 Org24598 治疗不会影响重新获得。当消退训练被可卡因自我给药或禁欲控制条件取代时，用相同剂量的 Org24598 治疗会导致重新获得，与在消退训练课程之前给予 Org24598 时观察到的重新获得相比，重新获得明显更快。结果支持 GlyT-1 抑制剂预处理与可卡因线索消退训练相结合抑制复发的潜在临床效用。
