Anxiolytic activity of NPY receptor agonists in the conflict test
Anxiolytic activity of NPY receptor agonists in the conflict test
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DOI：
10.1007/s002130050313
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发表时间：
1997-07-01
影响因子：
3.4
通讯作者：
Koob, G
中科院分区：
文献类型：
--
作者：
Britton, KT;Southerland, S;Koob, G
本研究探讨了受体亚型特异性和GABAa受体配体在npy诱导的应激刺激行为反应中的可能调节作用。首先，一系列NFY受体激动剂在递增性休克修正冲突试验中检验了它们对惩罚反应的潜在影响。NPY、肽YY （PYY）和NPY Y-1受体激动剂[Leu(31), Pro(34)]-NPY和[Gly(6), Glu(26), Lys(29), Pro(34)]-NPY在冲突试验中产生惩罚反应增加。对未受惩罚的反应没有显著影响。反应模式与苯二氮卓类激动剂氯二氮环氧化物相似。胰肽（PP）和Y-2激动剂NPY13-36或[Glu(2,32),Ala(6),Dpr(27),Lys(28)]-NPY均未显著改变惩罚或非惩罚反应。值得注意的是，非典型Y-1激动剂[Cys(7,21),Pro(34)]- NPY对惩罚反应的影响可以忽略不计，这与YI受体亚类的存在一致。其次，NPY的抗焦虑作用受到阻断GABAa受体复合物作用的治疗。苯二氮卓类拮抗剂氟马西尼并未改变NPY产生的惩罚反应的增加，仅被微毒素受体配体异丙基双环磷酸（10和15 μ g/kg）部分阻断。这些发现进一步支持了NPY抗焦虑样作用的药理学底物可能由Y-1受体亚型介导的假设，并表明这些作用不依赖于GABA/苯二氮卓受体复合物的苯二氮卓或微毒素结合位点。
This investigation examined receptor subtype specificity and possible modulation by GABAa receptor ligands of NPY-induced behavioral responses to stressful stimuli. First, a series of NFY receptor agonists were examined for their potential effects on punished responding in a conflict test modified for incremental shock. NPY, peptide YY (PYY) and NPY Y-1 receptor agonists [Leu(31), Pro(34)]-NPY and [Gly(6), Glu(26), Lys(29), Pro(34)]-NPY produced increases in punished responding in the conflict test. No significant effects on unpunished responding were noted. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP) nor the Y-2 agonists NPY13-36 or [Glu(2,32),Ala(6),Dpr(27),Lys(28)]-NPY significantly altered punished or unpunished responding. Of significance, the atypical Y-1 agonist [Cys(7,21),Pro(34)]- NPY produced negligible effects on punished responding, consistent with the presence of a subclass of YI receptors. Second, the anxiolytic effects of NPY were subjected to treatments that block actions at the GABAa receptor complex. The increase in punished responding produced by NPY was not altered by administration of the benzodiazepine antagonist flumazenil and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophosphate (10 and 15 mu g/kg). These findings further support the hypothesis that the pharmacologic substrates for the anxiolytic-like actions of NPY may be mediated by the Y-1 receptor subtype and suggest that these actions are independent of either the benzodiazepine or picrotoxinin binding sites of the GABA/benzodiazepine receptor complex.