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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >18-Methoxycoronaridine blocks context-induced reinstatement following cocaine self-administration in rats
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18-Methoxycoronaridine blocks context-induced reinstatement following cocaine self-administration in rats

机译：可卡因自我给药后18-甲氧基冠心苷阻滞上下文诱导的恢复

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Numerous studies utilizing drug self-administration have shown the importance of conditioned cues in maintaining and reinstating addictive behaviors. However, most used simple cues that fail to replicate the complexity of cues present in human craving and addiction. We have recently shown that music can induce behavioral and neurochemical changes in rats following classical conditioning with psychostimulants. However, such effects have yet to be characterized utilizing operant self-administration procedures, particularly with regard to craving and relapse. The goal of the present study was to validate the effectiveness of music as a contextual conditioned stimulus using cocaine in an operant reinstatement model of relapse. Rats were trained to lever press for cocaine with a musical cue, and were subsequently tested during reinstatement sessions to determine how musical conditioning affected drug seeking behavior. Additionally, in vivo microdialysis was used to determine basolateral amygdala involvement during reinstatement. Lastly, tests were conducted to determine whether the putative anti-addictive agent 18-methoxycoronaridine (18-MC) could attenuate cue-induced drug seeking behavior. Our results show that music-conditioned animals exhibited increased drug seeking behaviors when compared to controls during reinstatement test sessions. Furthermore, music-conditioned subjects exhibited increased extracellular dopamine in the basolateral amygdala during reinstatement sessions. Perhaps most importantly, 18-MC blocked musical cue-induced reinstatement. Thus, music can be a powerful contextual conditioned cue in rats, capable of inducing changes in both brain neurochemistry and drug seeking behavior during abstinence. The fact that 18-MC blocked cue-induced reinstatement suggests that α3β4 nicotinic receptors may be involved in the mechanism of craving, and that 18-MC may help prevent relapse to drug addiction in humans.
机译：利用药物自我管理的大量研究表明，条件提示在维持和恢复成瘾行为方面的重要性。但是，大多数使用的简单提示无法复制人类渴望和成瘾中存在的提示的复杂性。我们最近发现，在用精神刺激剂进行经典调节后，音乐可以诱发大鼠的行为和神经化学变化。但是，这种效果尚未通过使用有效的自我管理程序来表征，特别是在渴望和复发方面。本研究的目的是在可操作的复发恢复模型中使用可卡因验证音乐作为情境条件刺激的有效性。对大鼠进行了训练，使其具有音乐提示来压榨可卡因，随后在恢复阶段进行了测试，以确定音乐条件如何影响药物寻找行为。此外，体内微透析用于确定恢复过程中基底外侧扁桃体受累。最后，进行了测试以确定推定的抗上瘾剂18-甲氧基Coronaridine（18-MC）是否可以减弱提示诱导的寻药行为。我们的结果表明，在恢复测试阶段与对照组相比，有音乐条件的动物表现出增加的寻药行为。此外，在恢复阶段，受音乐条件限制的受试者的基底外侧杏仁核表现出细胞外多巴胺增加。也许最重要的是，18-MC阻止了音乐提示引起的恢复。因此，音乐可以是大鼠中强大的情境条件提示，能够诱导禁欲期间脑神经化学和寻求药物行为的变化。 18-MC阻止提示诱导的恢复的事实表明，α3β4烟碱样受体可能与渴望机制有关，而18-MC可能有助于防止人类吸毒成瘾的复发。

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