Jones T A, Schallert T
Department of Psychology, University of Texas, Austin 78712.
Behav Brain Res. 1992 Oct 31;51(1):1-13. doi: 10.1016/s0166-4328(05)80306-7.
Agents which enhance the activity of gamma-aminobutyric acid (GABA) can severely disrupt behavioral recovery in rats following damage to the neocortex if delivered during a sensitive postoperative period. The mechanisms of this disruption have not been found. It has been suggested previously that the ipsilateral striatum and related structures may be transiently disabled after cortical lesions and that diazepam may interfere with restoration of function in these areas. In the present experiment, the subcortical anatomical effects of chronic (3 weeks) administration of diazepam, an indirect GABAergic agonist, were assessed following unilateral lesions of the anteromedial cortex (AMC) or the sensorimotor cortex (SMC) in rats. Atrophic and degenerative changes were examined in the striatum, substantia nigra and thalamus. Following either AMC or SMC lesions, there was a reduction in the size of the ipsilateral striatum and thalamus and a loss of neurons in the ipsilateral substantia nigra pars reticulata (SNr). After AMC lesions, striatal atrophy and neuron loss in the SNr were increased by the diazepam regimen relative to vehicle-treated controls. In addition, diazepam interfered with the behavioral recovery from somatic-sensorimotor asymmetries in AMC-lesioned rats. After SMC lesions, the sites of striatal and thalamic atrophy were different from that observed after AMC lesions, and the extent of atrophy and neuron loss was not exaggerated by diazepam treatment. Consistent with these data, diazepam did not significantly affect recovery from SMC lesions. These findings suggest that the long-term disruptive effects of diazepam on recovery of function after AMC lesions may be related to an augmentation of lesion-induced degeneration.
如果在术后敏感时期给予增强γ-氨基丁酸（GABA）活性的药物，会严重干扰大鼠新皮质损伤后的行为恢复。这种干扰的机制尚未明确。此前有研究表明，皮质损伤后同侧纹状体及相关结构可能会暂时功能失调，而地西泮可能会干扰这些区域功能的恢复。在本实验中，研究了大鼠单侧前内侧皮质（AMC）或感觉运动皮质（SMC）损伤后，长期（3周）给予间接GABA能激动剂地西泮的皮质下解剖学效应。对纹状体、黑质和丘脑的萎缩及退行性变化进行了检查。在AMC或SMC损伤后，同侧纹状体和丘脑体积减小，同侧黑质网状部（SNr）神经元丢失。与给予赋形剂处理的对照组相比，AMC损伤后，地西泮处理组的纹状体萎缩和SNr神经元丢失增加。此外，地西泮干扰了AMC损伤大鼠躯体感觉运动不对称的行为恢复。SMC损伤后，纹状体和丘脑萎缩部位与AMC损伤后不同，地西泮处理并未加剧萎缩程度和神经元丢失。与这些数据一致，地西泮对SMC损伤后的恢复没有显著影响。这些发现表明，地西泮对AMC损伤后功能恢复的长期干扰作用可能与损伤诱导的变性增强有关。
