Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Neuropharmacology. 2013 Apr;67:326-30. doi: 10.1016/j.neuropharm.2012.11.021. Epub 2012 Dec 3.
We previously demonstrated the critical role of noradrenergic transmission within the ventral part of the bed nucleus of the stria terminalis (vBNST) in pain-induced aversion. We showed that activation of β-adrenoceptors in this brain region by intra-vBNST injection of isoproterenol, a β-adrenoceptor agonist, produced aversive responses. In the present study, we examined the effects of a β-adrenoceptor agonist injected into the vBNST on food intake and anxiety-like behaviors in male Sprague-Dawley rats. Bilateral intra-vBNST injection of isoproterenol (3 and 10 nmol/side) caused a dose-dependent decrease in food intake; this suppressive effect was reversed by co-administration of timolol, a β-adrenoceptor antagonist. Dose-dependent (10 and 30 nmol/side) induction of anxiety-like behaviors by isoproterenol was observed in the elevated plus maze (EPM) test, which was also reversed by co-administration of timolol. Off-site control injections of isoproterenol into the lateral ventricle did not show any significant effect in the food consumption and EPM tests. These results suggest that the vBNST is one of the neuroanatomical substrates which may be involved in the close relationship between negative affective states and reduction of food intake, and that noradrenergic transmission within this brain region plays a critical role in inducing anxiety-like behaviors and reduced food intake.
我们之前证明了终纹床核腹侧部(vBNST)内去甲肾上腺素传递在疼痛引起的厌恶中的关键作用。我们表明,通过向该脑区注射β-肾上腺素受体激动剂异丙肾上腺素激活β-肾上腺素受体,会产生厌恶反应。在本研究中,我们检查了将β-肾上腺素受体激动剂注射到 vBNST 中对雄性 Sprague-Dawley 大鼠的摄食和焦虑样行为的影响。双侧 vBNST 注射异丙肾上腺素(3 和 10 nmol/侧)会导致摄食量呈剂量依赖性下降;这种抑制作用可被β-肾上腺素受体拮抗剂 timolol 逆转。在高架十字迷宫(EPM)测试中观察到异丙肾上腺素(10 和 30 nmol/侧)剂量依赖性诱导焦虑样行为,timolol 的共同给药也可逆转这种行为。向侧脑室进行异位对照注射异丙肾上腺素在食物消耗和 EPM 测试中均未显示出任何显著影响。这些结果表明,vBNST 可能是参与负面情绪状态与摄食量减少之间密切关系的神经解剖学基础之一,并且该脑区的去甲肾上腺素传递在诱导焦虑样行为和减少摄食方面起着关键作用。