Cocaine-taking and cocaine-seeking behaviors in rats remain stable after systemic administration of GYKI 52466: a non-competitive AMPA receptor antagonist.
Cocaine-taking and cocaine-seeking behaviors in rats remain stable after systemic administration of GYKI 52466: a non-competitive AMPA receptor antagonist.
复制标题
全身给予 GYKI 52466（一种非竞争性 AMPA 受体拮抗剂）后，大鼠的可卡因服用和可卡因寻求行为保持稳定。
DOI：
10.1016/j.neulet.2011.12.028
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发表时间：
2012
影响因子：
2.5
通讯作者：
Gardner,EliotL
中科院分区：
文献类型：
--
作者：
Srivastava,Ratika;Xi,Zheng-Xiong;Gardner,EliotL
鉴于AMPA介导的突触传递增强在药物寻求复发中的作用，我们研究了全身给药AMPA受体拮抗剂GYKI 52466是否能抑制大鼠的可卡因摄入和可卡因寻求行为。训练大鼠自我服用可卡因，直到达到稳定的自我给药。评估GYKI 52466（1、3或10mg/kg，静脉注射）对可卡因自我给药的影响。允许动物重新建立稳定的可卡因自我管理，然后在行为上停止吸毒。评估GYKI 52466 （3,10 mg/kg，静脉注射）对可卡因诱导的药物寻求行为恢复的影响。我们发现GYKI 52466在自我给药和复吸范式中均未能抑制可卡因吸食和可卡因寻求。我们认为，尽管AMPA受体可能参与可卡因奖励和成瘾，但AMPA受体拮抗剂GYKI 52466对可卡因成瘾的治疗潜力较低。
Given the posited role of enhanced AMPA-mediated synaptic transmission in relapse to drug seeking, we investigated whether systemic administration of the AMPA receptor antagonist GYKI 52466 inhibits cocaine-taking and cocaine-seeking behavior in rats. Rats were trained to self-administer cocaine until stable self-administration was achieved. Effects of GYKI 52466 (1, 3, or 10mg/kg, i.v.) on cocaine self-administration were assessed. Animals were allowed to re-establish stable cocaine self-administration and were then behaviorally extinguished from drug taking. The effects of GYKI 52466 (3, 10mg/kg, i.v.) on cocaine-induced reinstatement of drug-seeking behavior were assessed. We found that GYKI 52466 failed to inhibit cocaine-taking and cocaine-seeking in both the self-administration and reinstatement paradigms. We suggest that although AMPA receptors may be involved in cocaine reward and addiction, the AMPA receptor antagonist GYKI 52466 has low therapeutic potential for cocaine addiction treatment.