A role for neuropeptide Y Y5 but not the Y1-receptor subtype in food deprivation-induced reinstatement of heroin seeking in the rat
A role for neuropeptide Y Y5 but not the Y1-receptor subtype in food deprivation-induced reinstatement of heroin seeking in the rat
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DOI：
10.1007/s00213-011-2362-9
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发表时间：
2011-06
影响因子：
3.4
通讯作者：
Tia Maric;F. Sedki;Danielle Chafetz;Nick Schoela;U. Shalev
中科院分区：
文献类型：
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作者：
Tia Maric;F. Sedki;Danielle Chafetz;Nick Schoela;U. Shalev
理性和目的神经肽Y （NPY）是一种摄氧肽，在食物限制期间释放，已被证明对药物相关行为具有重要的调节作用。我们之前报道过急性食物剥夺（FD）和NPY注射都可以恢复已经消失的药物寻求行为，这是一种药物滥用复发的动物模型。然而，目前尚不清楚FD对药物寻找的影响是否依赖于NPY的传播。在这里，我们使用恢复模型来评估NPY Y1和y5受体介导的传递在fd诱导的海洛因寻求恢复中的作用。方法训练大鼠自我给药（0.1 mg/kg/滴注/静脉注射）10 ~ 12 d。然后动物在21小时FD和饱和条件下进行灭绝训练，然后进行药物寻求恢复试验。结果注射一种新型NPY y5受体拮抗剂Lu AA33810（0.0、1.0或30.0 mg/kg/IP）可显著减弱fd诱导的消失的海洛因寻求恢复。然而，y1受体拮抗剂BIBO 3304（0.0、5.0或10.0 nmol/脑室内）对恢复没有显著影响。结论通过NPY - Y1受体介导的信号在海洛因寻求行为的恢复中起着适度的作用，而Y5受体的激活在fd诱导的海洛因寻求行为恢复中起着关键作用。
Rational and objectivesNeuropeptide Y (NPY), an orexigenic peptide that is released during periods of food restriction, has been shown to have a significant modulatory impact on drug-related behaviors. We have previously reported that both acute food deprivation (FD) and NPY injections can reinstate extinguished drug-seeking behavior, a proposed animal model of relapse to drug abuse. However, it is not clear whether the FD effect on drug seeking is dependent on NPY transmission. Here, we used the reinstatement model to assess the role of NPY Y1 and Y5-receptor-mediated transmission in FD-induced reinstatement of heroin seeking.MethodsRats were trained to self-administer heroin for 10–12 days (0.1 mg/kg/infusion/intravenous). Animals then underwent extinction training followed by drug-seeking reinstatement tests under 21 h of FD and sated conditions.ResultsInjections of a novel NPY Y5-receptor antagonist, Lu AA33810 (0.0, 1.0, or 30.0 mg/kg/IP), resulted in a significant attenuation of FD-induced reinstatement of extinguished heroin seeking. However, no significant effects on reinstatement were found for the Y1-receptor antagonist, BIBO 3304 (0.0, 5.0, or 10.0 nmol/intracerebroventricular).ConclusionsThese results suggest that while signals mediated through NPY Y1 receptors play a modest role in reinstatement, activation of Y5 receptors has a critical function in FD-induced reinstatement of heroin-seeking behavior.