首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Reduction of opioid dependence by the CB1 antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction
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Reduction of opioid dependence by the CB1 antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction

机译:CB1拮抗剂SR141716A在小鼠中减少阿片类药物依赖性:对阿片类药物成瘾药物治疗的兴趣评估

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class="enumerated" style="list-style-type:decimal">Several compounds, mainly opioid agonists such as methadone, are currently used for long term medication of heroin addicts. Nevertheless, these maintenance treatments have the disadvantage to induce a dependence to another opiate. As interactions between opioid and cannabinoid systems have been demonstrated, the ability of the CB1 antagonist, SR141716A to reduce morphine-induced addiction was investigated.The effects of SR141716A on the rewarding responses of morphine were evaluated in the place conditioning paradigm. No significant conditioned preference or aversion were observed after repeated treatment with the CB1 antagonist alone. However, SR141716A was able to antagonize the acquisition of morphine-induced conditioned place preference.SR141716A was co-administered with morphine for 5 days, and the withdrawal syndrome was precipitated by naloxone administration. A reduction in the incidence of two main signs of abstinence: wet dog shakes and jumping was observed while the other were not significantly modified. In contrast, an acute injection of the CB1 antagonist just before naloxone administration was unable to modify the incidence of the behavioural manifestations of the withdrawal, suggesting that only chronic blockade of CB1 receptors is able to reduce morphine-induced physical dependence.Several biochemical mechanisms could explain the reduction of opioid dependence by CB1 antagonists. Whatever the hypotheses, this study supports the reported interaction between the endogenous cannabinoid and opioid systems, and suggests that SR 141716A warrants further investigations for a possible use in opioid addiction.
机译:class =“ enumerated” style =“ list-style-type:decimal”> <!-list-behavior =枚举前缀-word = mark-type = decimal max-label-size = 0-> 几种化合物,主要是阿片类激动剂,如美沙酮,目前用于海洛因成瘾者的长期药物治疗。然而,这些维持治疗的缺点是引起对另一鸦片的依赖性。通过证明阿片类药物与大麻素系统之间的相互作用,研究了CB1拮抗剂SR141716A减少吗啡诱导的成瘾的能力。 在该位置评估了SR141716A对吗啡奖励反应的影响。条件范式。单独使用CB1拮抗剂反复治疗后,未观察到明显的条件偏爱或厌恶感。但是,SR141716A能够拮抗吗啡诱导的条件性位置偏爱的获得。 SR141716A与吗啡并用5天,纳洛酮使戒断综合征加重。禁欲的两个主要症状的发生率降低:观察到湿狗摇动和跳跃,而其他没有明显改变。相比之下,在纳洛酮给药前立即注射CB1拮抗剂并不能改变戒断行为表现的发生率,这表明只有慢性阻断CB1受体才能降低吗啡诱导的身体依赖性。几种生化机制可以解释CB1拮抗剂对阿片类药物依赖性的降低。无论哪种假设,这项研究都支持报道的内源性大麻素和阿片类药物系统之间的相互作用,并建议SR 141716A值得进一步研究,以探讨阿片类药物成瘾的可能用途。

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