Werkheiser Jennifer L, Rawls Scott M, Cowan Alan
Department of Pharmacology, Temple University Health Sciences Center, PA, Philadelphia, USA.
Neuropharmacology. 2007 Mar;52(3):925-30. doi: 10.1016/j.neuropharm.2006.10.010. Epub 2006 Dec 5.
Icilin, a cooling compound, produces vigorous wet-dog shakes in rats. We have reported previously that icilin-induced wet-dog shakes are blocked by the kappa opioid receptor agonists, nalfurafine and U50,488H, and that icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum. Since activation of kappa opioid receptors inhibits glutamate release intrastriatally, we targeted glutamate release within the dorsal striatum using nalfurafine and examined the role of the dorsal striatum in icilin-induced wet-dog shakes, more specifically, the effect that icilin-evoked intrastriatal glutamate release has on the overt stimulant behavior. We report that nalfurafine (0.04mg/kg) inhibits icilin (0.50mg/kg)-induced wet-dog shakes and that this inhibition is reversed by intrastriatal perfusion of the kappa opioid receptor antagonist, norbinaltorphimine (100nM). Furthermore,we antagonized icilin-evoked glutamate release with nalfurafine (0.04mg/kg), and reversed inhibition of glutamate release with intrastriatal norbinaltorphimine (100nM). These findings support a central component in the behavioral response to icilin and suggest that activation of kappa opioid receptors antagonizes icilin-induced wet-dog shakes in rats by inhibiting glutamate release within the dorsal striatum.
冰莲素是一种清凉化合物，能使大鼠剧烈地做出像被水淋湿的狗那样抖动身体的动作。我们之前报道过，冰莲素诱发的像被水淋湿的狗那样抖动身体的动作会被κ阿片受体激动剂纳呋拉啡和U50,488H阻断，并且冰莲素会使背侧纹状体内的谷氨酸呈剂量和时间依赖性增加。由于κ阿片受体的激活会抑制纹状体内谷氨酸的释放，我们使用纳呋拉啡来靶向背侧纹状体内的谷氨酸释放，并研究背侧纹状体在冰莲素诱发的像被水淋湿的狗那样抖动身体的动作中所起的作用，更具体地说，就是研究冰莲素诱发的纹状体内谷氨酸释放对明显的兴奋行为的影响。我们报告称，纳呋拉啡（0.04毫克/千克）能抑制冰莲素（0.50毫克/千克）诱发的像被水淋湿的狗那样抖动身体的动作，并且这种抑制作用会被纹状体内灌注κ阿片受体拮抗剂 norbinaltorphimine（100纳摩尔）逆转。此外，我们用纳呋拉啡（0.04毫克/千克）拮抗冰莲素诱发的谷氨酸释放，并用纹状体内的norbinaltorphimine（100纳摩尔）逆转对谷氨酸释放的抑制。这些发现支持了对冰莲素行为反应中的一个核心成分，并表明κ阿片受体的激活通过抑制背侧纹状体内的谷氨酸释放来拮抗大鼠中冰莲素诱发的像被水淋湿的狗那样抖动身体的动作。
