(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.
(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.
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DOI：
10.1016/j.drugalcdep.2018.04.030
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发表时间：
2018-08-01
影响因子：
4.2
通讯作者：
Ranaldi R
中科院分区：
文献类型：
--
作者：
Manuszak M;Harding W;Gadhiya S;Ranaldi R
多巴胺受体与可卡因的奖励和寻找有关。我们假设(−)-stepholidine是一种多巴胺D1/D2/D3多受体药物，在动物模型中可以有效地减少可卡因的奖励和寻找。我们研究了(−)-stepholidine在线索诱导的可卡因寻求和可卡因自我给药（奖励）恢复中的作用。提示诱导恢复实验：训练大鼠连续15次按下可卡因（1 mg/kg/注射）强化的杠杆，之后通过保留可卡因和可卡因配对提示（光和泵激活）来消除反应。随后进行了线索诱导恢复测试，受试者暴露于两个可卡因线索呈现，并按下活动杠杆产生线索。在恢复试验之前，受试者接受四种(−)-斯蒂芬定剂量中的一种治疗。可卡因自我给药（奖励）实验：采用递进比例强化法训练大鼠自我给药。在稳定断点建立后，在测试前给大鼠注射四剂量的(−)-stepholidine；每次剂量的注射都是在单独的测试阶段之前进行的，没有治疗阶段的干预以重新建立断点。（−）-Stepholidine以剂量相关的方式显著降低线索诱导的可卡因寻求恢复。此外，(−)-stepholidine显著降低了可卡因奖励的断点。（−）-Stepholidine对运动活动无显著影响。（−）-Stepholidine减少线索诱导的可卡因寻求和可卡因奖励的恢复，表明它可能对治疗可卡因成瘾复发有用。
Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (−)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (−)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (−)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (−)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. (−)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (−)-stepholidine significantly reduced break points for cocaine reward. (−)-Stepholidine did not significantly affect locomotor activity. (−)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction.
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影响因子：
3.4
作者：
Galaj, E.;Harding, W.;Ranaldi, R.
通讯作者：
Ranaldi, R.
影响因子：
3.4
作者：
Haney, M;Ward, AS;Fischman, MW
通讯作者：
Fischman, MW
影响因子：
3.3
作者：
LeMoine, C;Bloch, B
通讯作者：
Bloch, B
影响因子：
4.2
作者：
Figueroa-Guzman, Yazmin;Mueller, Christopher;Vranjkovic, Oliver;Wisniewski, Samantha;Yang, Zheng;Li, Shi-Jiang;Bohr, Colin;Graf, Evan N.;Baker, David A.;Mantsch, John R.
通讯作者：
Mantsch, John R.
影响因子：
5
作者：
Hicks, Callum;Huang, Peng;Liu-Chen, Lee-Yuan
通讯作者：
Liu-Chen, Lee-Yuan