Roland B L, Grijalva C V
Department of Psychology and Brain Research Institute, University of California, Los Angeles 90024.
Brain Res. 1993 Mar 5;605(1):110-20. doi: 10.1016/0006-8993(93)91362-v.
Electrolytic lateral hypothalamic (LH) lesions produce numerous disorders including aphagia, gastric mucosal erosions and autonomic and sensorimotor dysfunctions. This series of experiments examined whether damage to LH neurons or dopaminergic fibers of passage produce similar forms and severity of gastric erosions, as well as other disorders. In Experiment 1, LH neurons were destroyed by the excitatory neurotoxin, kainic acid, that presumably leaves axonal fibers of passage intact. Relatively selective damage to LH neurons with kainic acid produced glandular gastric erosions, as well as sensorimotor and autonomic dysfunctions similar to those seen following electrolytic LH lesions. This suggests that direct damage to LH cell bodies may be a primary cause of many of the disorders observed following LH lesions. In Experiments 2 and 3, electrolytic lesions were used to destroy cell bodies in the substantia nigra and their dopaminergic fibers (some of which pass through the LH area). This resulted in the production of gastric erosions in the absence of significant autonomic dysfunctions. Furthermore, atropine methylnitrate prevented the occurrence of gastric erosions following substantia nigra lesions, suggesting that the erosion formation is mediated via parasympathetic-vagal activity. In contrast, destruction of the ventral tegmental area (and its associated dopaminergic fibers) had no significant effect on gastric erosion formation. Experiment 4 showed that apomorphine, a central and peripheral dopamine agonist, provided protection against LH lesion-induced gastric erosion formation, whereas domperidone, a peripheral dopamine antagonist, had no effect. Taken together, this study suggests that (a) both LH neurons and fibers of passage provide a potential anatomical basis for the development of gastric mucosal erosions, (b) that an alteration in dopamine levels, either centrally or peripherally, may represent an important neurochemical mechanism for the development of erosions, and (c) that the occurrence of gastric erosion can be dissociated from other symptoms of the LH syndrome.
电解损毁下丘脑外侧区（LH）会引发多种紊乱，包括拒食、胃黏膜糜烂以及自主神经和感觉运动功能障碍。这一系列实验研究了损毁LH神经元或其通过的多巴胺能纤维是否会产生相似类型和严重程度的胃糜烂以及其他紊乱。在实验1中，使用兴奋性神经毒素红藻氨酸损毁LH神经元，推测该毒素可使通过的轴突纤维保持完整。用红藻氨酸对LH神经元进行相对选择性损毁会导致腺性胃糜烂，以及与电解损毁LH后所见相似的感觉运动和自主神经功能障碍。这表明对LH细胞体的直接损伤可能是LH损毁后所观察到的许多紊乱的主要原因。在实验2和实验3中，采用电解损毁来破坏黑质中的细胞体及其多巴胺能纤维（其中一些纤维穿过LH区域）。这导致在没有明显自主神经功能障碍的情况下产生胃糜烂。此外，甲基硝酸阿托品可预防黑质损毁后胃糜烂的发生，这表明糜烂的形成是通过副交感神经 - 迷走神经活动介导的。相比之下，损毁腹侧被盖区（及其相关的多巴胺能纤维）对胃糜烂的形成没有显著影响。实验4表明，中枢和外周多巴胺激动剂阿扑吗啡可预防LH损毁诱导的胃糜烂形成，而外周多巴胺拮抗剂多潘立酮则没有效果。综上所述，本研究表明：（a）LH神经元及其通过的纤维均为胃黏膜糜烂的发生提供了潜在的解剖学基础；（b）中枢或外周多巴胺水平的改变可能是糜烂发生的重要神经化学机制；（c）胃糜烂的发生可与LH综合征的其他症状相分离。
