Hayes Matthew R, Covasa Mihai
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802-6504, USA.
Brain Res. 2006 May 9;1088(1):120-30. doi: 10.1016/j.brainres.2006.03.018. Epub 2006 Apr 21.
The combination of gastric distension and cholecystokinin (CCK) enhances both suppression of food intake and induction of c-Fos-like immunoreactivity (Fos-LI) in the dorsal vagal complex (DVC). Previously, we have shown that serotonin type-3 (5-HT3) receptor mediation of suppression of food intake by CCK requires gastric participation. Therefore, we hypothesized that 5-HT3 receptors mediate CCK-induced Fos-LI in the dorsal hindbrain through a mechanism that involves gastric distension. To test this hypothesis, we counted Fos-LI in the DVC of ondansetron (1 mg/kg; 5-HT3 receptor antagonist) and vehicle-treated rats following gastric balloon distension (5 ml), CCK (1 microg/kg) administration, or CCK combined with gastric distension. Ondansetron administration attenuated DVC Fos-LI by CCK administration. Likewise, ondansetron attenuated Fos-LI by gastric distension in the DVC, specifically within the nucleus of the solitary tract (NTS) and area postrema (AP) nuclei. The most pronounced attenuation of distension-induced Fos-LI by ondansetron occurred in the NTS, particularly in the medial and intermedial NTS. When combined, CCK and gastric distension enhanced Fos-LI in the DVC greater than each treatment alone. Furthermore, ondansetron administration attenuated the overall DVC enhanced Fos-LI induced by CCK + gastric distension, in particular at the NTS and AP nuclei. We found that, within the mid-to-caudal regions of the NTS and AP, 5-HT3 receptors most significantly mediate neuronal activation by CCK + distension. In conjunction with previous behavioral data, these results show that gastric distension enhances CCK-induced neuronal activation in the DVC by activating 5-HT3 receptors.
胃扩张与胆囊收缩素（CCK）联合使用可增强对食物摄入的抑制作用，并诱导迷走神经背侧复合体（DVC）中c-Fos样免疫反应性（Fos-LI）的产生。此前，我们已经表明，CCK抑制食物摄入的过程中，5-羟色胺3型（5-HT3）受体的介导作用需要胃的参与。因此，我们推测5-HT3受体通过一种涉及胃扩张的机制介导CCK诱导的延髓后区Fos-LI的产生。为了验证这一假设，我们对昂丹司琼（1mg/kg；5-HT3受体拮抗剂）处理组和对照组大鼠在胃球囊扩张（5ml）、注射CCK（1μg/kg）或CCK与胃扩张联合处理后，计数DVC中的Fos-LI。注射昂丹司琼可减弱CCK注射引起的DVC Fos-LI。同样，昂丹司琼可减弱胃扩张引起的DVC中的Fos-LI，特别是在孤束核（NTS）和最后区（AP）核内。昂丹司琼对扩张诱导的Fos-LI的最显著减弱作用发生在NTS，特别是在内侧和中间内侧NTS。联合使用时，CCK和胃扩张比单独使用每种处理方法更能增强DVC中的Fos-LI。此外，注射昂丹司琼减弱了CCK+胃扩张诱导的DVC中总体增强的Fos-LI，特别是在NTS和AP核处。我们发现，在NTS和AP的中尾区域内，5-HT3受体最显著地介导CCK+扩张引起的神经元激活。结合先前的行为学数据，这些结果表明胃扩张通过激活5-HT3受体增强了CCK诱导的DVC神经元激活。
