Harik S I, Duckrow R B, LaManna J C, Rosenthal M, Sharma V K, Banerjee S P
J Neurosci. 1981 Jun;1(6):641-9. doi: 10.1523/JNEUROSCI.01-06-00641.1981.
The long term effects of specific noradrenergic denervation of rat cerebral cortex were considered in parallel studies of in vitro noradrenergic receptor binding and isoproterenol-induced adenosine 3':5'-monophosphate (cycle AMP) generation and of in vivo oxidative metabolism. Noradrenergic denervation was achieved by the local, unilateral injection of 6-hydroxydopamine into the locus ceruleus. Cerebral noradrenaline remained depleted throughout the 8-week duration of the study. Ligand-binding assays showed increased beta-adrenergic receptors 2 weeks after locus ceruleus lesion with recovery occurring by 4 weeks. There were no changes in alpha 1-adrenergic receptors. Isoproterenol-induced cyclic AMP generation increased at 2 weeks after lesion but recovered at 8 weeks. Dual wavelength reflection spectrophotometric measurements of cytochrome oxidase reduction/oxidation and local blood volume shifts, provoked in situ by direct cortical stimulation, also demonstrated abnormalities at 2 weeks with recovery by 4 weeks after lesion. Thus, in vivo and in vitro changes after locus ceruleus lesion are reversible and the time course of these changes is related temporally. These data suggest that cerebral cortex has adaptive capabilities which are activated to compensate for prolonged noradrenaline depletion. We also speculate that there may be a causal relationship between the in vitro and in vivo parameters studied.
在体外去甲肾上腺素能受体结合、异丙肾上腺素诱导的3':5'-单磷酸腺苷（环磷酸腺苷）生成以及体内氧化代谢的平行研究中，考虑了大鼠大脑皮质特定去甲肾上腺素能去神经支配的长期影响。通过向蓝斑局部单侧注射6-羟基多巴胺实现去甲肾上腺素能去神经支配。在整个8周的研究期间，大脑中的去甲肾上腺素一直处于耗竭状态。配体结合试验显示，蓝斑损伤后2周β-肾上腺素能受体增加，4周时恢复。α1-肾上腺素能受体无变化。损伤后2周异丙肾上腺素诱导的环磷酸腺苷生成增加，但8周时恢复。通过直接皮质刺激在原位引发的细胞色素氧化酶还原/氧化和局部血容量变化的双波长反射分光光度测量也显示，损伤后2周出现异常，4周时恢复。因此，蓝斑损伤后的体内和体外变化是可逆的，这些变化的时间进程在时间上相关。这些数据表明大脑皮质具有适应性能力，可被激活以补偿长期的去甲肾上腺素耗竭。我们还推测，所研究的体外和体内参数之间可能存在因果关系。
