• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum.
【24h】

Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum.

机译：P物质和胆囊收缩素调节纹状体对可卡因和甲基苯丙胺的神经化学反应。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The mechanism of action of drugs of abuse like cocaine and amphetamines has been studied extensively in the dopamine terminal field areas of the caudate-putamen (CPu) and the nucleus accumbens (NAc) of the rodent brain. These brain regions contain several neuropeptides that must play important roles in the normal physiological functions of these brain regions. The study of neuropeptide physiology in the context of the neurobiological responses to drugs of abuse may shed some light on the intrinsic mechanism of action of neuropeptides of the CPu and the NAc. The neuropeptides substance P (SP) and cholecystokinin (CCK) are present in the striatum where they could play an important role regulating the effects of psychostimulants like cocaine and amphetamines (methamphetamine [METH] is a long acting derivative of d-amphetamine). These highly addictive agents induce the release of dopamine (DA) (and other catecholamines) from dopaminergic terminals of the striatum. The excessive release of DA in the striatum and the NAc has been implicated in the habit-forming properties of these drugs. In order to study the contribution of SP and CCK in the striatum during psychostimulant treatment, we employed selective non-peptide neurokinin-1 (NK-1) and cholecystokinin-2 (CCK-2) receptor antagonists that readily cross the blood brain barrier. We infused the neurokinin-1 receptor (NK-1R) antagonist, L-733,060, into the striatum of freely moving rats via a microdialysis probe in order to assess the effects of SP on cocaine-induced DA overflow in the striatum. Infusion of the NK-1R antagonist prior to a systemic injection of cocaine (10 mg/kg i.p.) significantly attenuated DA overflow in the striatum. Conversely, infusion of a CCK-2 receptor (CCK-2R) antagonist, L-369,293, through the microdialysis probe evoked DA overflow in the striatum in the absence of cocaine and potentiated DA overflow after a single injection of cocaine (10 mg/kg i.p.). Exposure to METH (10 mg/kg 4x at two-hour intervals) produced deficits of dopamine transporters (DAT) in mice striatum that are detectable three days after the treatment and are long lasting. Pre-treatment (i.p. injections) with the NK-1R antagonist, WIN-51,708 30 minutes before the 1st and 4th injections of METH prevented the loss of DAT in the striatum. Moreover, pre-treatment with the NK-1R antagonist prevents METH-induced cell death. Taken together, these results demonstrate that the NK-1R and the CCK-2R are important modulators of the actions of the psychostimulants cocaine and METH. Neuropeptide receptors represent an important control point mediating the effects of the neurotransmitter DA in the striatum of the rodent brain.
机译：可卡因和苯丙胺等滥用药物的作用机理已在啮齿动物脑的尾状-丘脑（CPu）和伏伏核（NAc）的多巴胺末端区域进行了广泛研究。这些大脑区域包含一些神经肽，这些神经肽必须在这些大脑区域的正常生理功能中发挥重要作用。在对滥用药物的神经生物学反应方面对神经肽生理学的研究可能会为CPu和NAc的神经肽的内在作用机理提供一些启示。纹状体中存在神经肽物质P（SP）和胆囊收缩素（CCK），它们在调节精神兴奋剂（如可卡因和苯丙胺）的作用中起重要作用（甲基苯丙胺[METH]是d-苯丙胺的长效衍生物）。这些高度上瘾的药物诱导纹状体的多巴胺能末端释放多巴胺（DA）（和其他儿茶酚胺）。纹状体和NAc中DA的过度释放与这些药物的习惯形成特性有关。为了研究精神兴奋剂治疗期间纹状体中SP和CCK的贡献，我们采用了选择性非肽神经激肽1（NK-1）和胆囊收缩素2（CCK-2）受体拮抗剂，它们很容易穿过血脑屏障。我们通过微透析探针将神经激肽-1受体（NK-1R）拮抗剂L-733060注入自由活动大鼠的纹状体中，以评估SP对可卡因诱导的纹状体DA溢出的影响。在全身注射可卡因（10 mg / kg腹腔注射）之前输注NK-1R拮抗剂可显着减轻纹状体中的DA溢出。相反，在没有可卡因的情况下，通过微透析探针向CCK-2受体（CCK-2R）拮抗剂L-369,293注入会引起纹状体中的DA溢出，单次注射可卡因（10 mg / kg后，增强的DA溢出） ip）。暴露于METH（每隔2小时间隔10 mg / kg 4x）会在小鼠纹状体中产生多巴胺转运蛋白（DAT）缺陷，这种缺陷在治疗后三天即可检测到并且持续很长时间。在第1次和第4​​次METH注射之前30分钟用NK-1R拮抗剂WIN-51,708进行预处理（腹腔注射）可防止纹状体中DAT的损失。此外，用NK-1R拮抗剂进行预处理可防止METH诱导的细胞死亡。两者合计，这些结果表明，NK-1R和CCK-2R是可调节精神药物可卡因和METH作用的重要调节剂。神经肽受体代表着重要的控制点，介导啮齿类动物脑纹状体中神经递质DA的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号