The CB1 antagonist rimonabant (SR141716) blocks cue-induced reinstatement of cocaine seeking and other context and extinction phenomena predictive of relapse.
The CB1 antagonist rimonabant (SR141716) blocks cue-induced reinstatement of cocaine seeking and other context and extinction phenomena predictive of relapse.
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DOI：
10.1016/j.drugalcdep.2009.07.002
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Walker EA
中科院分区：
文献类型：
--
作者：
Ward SJ;Rosenberg M;Dykstra LA;Walker EA
大麻素 CB1 拮抗剂可减少动物对美味食物和几种滥用药物的自我管理，并调节条件性恐惧反应的消失。然而，关于 CB1 拮抗剂是否以及如何调节食欲行为的消失，人们知之甚少。因此，本研究检查了 CB1 受体拮抗剂利莫那班 (SR141716) 在可卡因或可口食物（玉米油或 Ensure）维持的反应消失过程中的影响，以及与可卡因呈现（即提示诱导恢复）或启动（可卡因或食物呈现）配对的刺激线索引起的反应。还检查了利莫那班对经过自我饮水训练的缺水小鼠的高反应率的影响。在小鼠自我给药可卡因中，利莫那班减弱了提示诱导的可卡因自我给药恢复，即可卡因消退期间的最初反应爆发和自发恢复期间的反应。在自我施用玉米油的小鼠中，利莫那班降低了灭绝期间的反应，并且还减弱了通过玉米油的启动作用而恢复的反应。此外，与媒介物治疗的小鼠相比，用利莫那班治疗的小鼠每天需要更少的疗程来达到可卡因维持反应消失的标准。此外，利莫那班对在 FR5 强化方案下训练对水做出反应的小鼠的操作反应率没有影响。总而言之，这些数据表明，除了减弱可口食物和滥用药物的主要强化作用外，CB1受体拮抗作用还可以减弱消退学习过程中的背景和线索反应性，并可能以这种方式增强消退学习。
Cannabinoid CB1 antagonists decrease self-administration of palatable food and several abused drugs in animals and modulate extinction of conditioned fear responses. Less is known, however, about whether and how CB1 antagonists might modulate the extinction of appetitive behavior. Therefore, this study examined the effects of the CB1 receptor antagonist rimonabant (SR141716) during extinction of responding maintained either by cocaine or by palatable foods (corn oil or Ensure), as well as responding elicited by stimulus cues that had been paired with the presentation of cocaine (i.e., cue-induced reinstatement) or a prime (presentation of cocaine or food). The effect of rimonabant on high rate responding in water-deprived mice trained to self-administer water was also examined. In mice self-administering cocaine, rimonabant attenuated cue-induced reinstatement of cocaine self-administration, the initial burst of responding during cocaine extinction and responding during spontaneous recovery. In mice self-administering corn oil, rimonabant decreased responding during extinction and also attenuated responding that had been reinstated by a priming presentation of corn oil. Moreover, mice treated with rimonabant required fewer daily sessions to reach criterion for extinction of cocaine-maintained responding than vehicle treated mice. Also, rimonabant had no effect on rate of operant responding in mice trained to respond for water under an FR5 schedule of reinforcement. Taken together, these data suggest that in addition to attenuating the primary reinforcing effects of both palatable foods and drugs of abuse, CB1 receptor antagonism can attenuate context and cue reactivity during extinction learning and potentially enhance extinction learning in this way.
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影响因子：
2
作者：
Harloe, John P.;Thorpe, Andrew J.;Lichtman, Aron H.
通讯作者：
Lichtman, Aron H.
影响因子：
3.4
作者：
Niyuhire, Floride;Varvel, Stephen A.;Lichtman, Aron H.
通讯作者：
Lichtman, Aron H.
影响因子：
3.4
作者：
Higgs, S;Williams, CM;Kirkham, TC
通讯作者：
Kirkham, TC
影响因子：
5.3
作者：
BUTTER, CM;MISHKIN, M;ROSVOLD, HE
通讯作者：
ROSVOLD, HE
影响因子：
3.4
作者：
Caine, SB;Negus, SS;Mello, NK
通讯作者：
Mello, NK