...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Addiction biology >Activation of glucagon-like peptide-1 receptors in the nucleus accumbens attenuates cocaine seeking in rats
【24h】

Activation of glucagon-like peptide-1 receptors in the nucleus accumbens attenuates cocaine seeking in rats

机译：在核心中的胰高血糖素样肽-1受体的激活衰减在大鼠中寻求的可卡因

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

Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors reduces cocaine-mediated behaviors and cocaine-evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP-1 receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP-1 receptor agonist exendin-4 penetrated the brain and localized with neurons and astrocytes in the NAc. Administration of exendin-4 directly into the NAc core and shell subregions significantly attenuated cocaine priming-induced reinstatement of drug-seeking behavior. These effects were not due to deficits in operant responding or suppression of locomotor activity as intra-accumbal exendin-4 administration had no effect on sucrose-seeking behavior. To determine the effects of GLP-1 receptor activation on neuronal excitability, exendin-4 was bath applied to ex vivo NAc slices from cocaine-experienced and saline-experienced rats following extinction of cocaine-taking behavior. Exendin-4 increased the frequency of action potential firing of NAc core and shell medium spiny neurons in cocaine-experienced rats while no effect was observed in saline controls. In contrast, exendin-4 did not affect the frequency or amplitude of spontaneous excitatory postsynaptic currents or alter the paired-pulse ratios of evoked excitatory postsynaptic currents. These effects were not associated with altered expression of GLP-1 receptors in the NAc following cocaine self-administration. Taken together, these findings indicate that increased activation of GLP-1 receptors in the NAc during cocaine abstinence increases intrinsic, but not synaptic, excitability of medium spiny neurons and is sufficient to reduce cocaine-seeking behavior.
机译：最近的证据表明胰高血糖素样肽-1（GLP-1）受体的激活可降低Cocaine介导的行为和Cocaine诱发的多巴胺释放在细胞核中（NAC）。然而，没有研究过NAC GLP-1受体在恢复可卡因寻求行为中的作用，复发动物模型。在这里，我们表明，全身输注相对于GLP-1受体激动剂Exendin-4的行为相关剂量渗透脑并用Nac中的神经元和星形胶质细胞局部。将Exendin-4直接施用于NAC核心和壳次区域显着减弱了可卡因灌注诱导的药物寻求行为恢复。由于组织内抗蛋白-4给药，因此，这些效果不是由于操作症的响应或抑制运动活性的缺陷，对蔗糖寻求行为没有影响。为了确定GLP-1受体激活对神经元兴奋性的影响，Exendin-4沐浴涂给来自可卡因采取行为后的可卡因和盐水经验的大鼠的离体NAC切片。 exendin-4增加了在可卡因经验丰富的大鼠中Nac核心和壳中刺神经元的作用潜力射击的频率，而在盐水对照中没有观察到效果。相反，exendin-4不会影响自发兴奋性突触电流的频率或幅度，或者改变诱发兴奋性突触突触电流的配对脉冲比。这些效应与NAC在可卡因自我给药后NAC中的GLP-1受体的表达无关。总之，这些发现表明，在可卡因禁欲期间，在NAC期间增加了GLP-1受体的激活增加了内在的，但不是突触的中等刺神经元的兴奋性，并且足以降低寻​​求可卡因的行为。

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