Bardgett M E, Jackson J L, Taylor G T, Csernansky J G
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Behav Brain Res. 1995 Oct;70(2):153-64. doi: 10.1016/0166-4328(95)80005-0.
Intracerebroventricular (i.c.v.) administration of kainic acid (KA) produces graded neuronal loss in the hippocampus and other regions of the medial temporal lobe. Many of these brain regions send excitatory projections to the nucleus accumbens, a dopaminergic brain area implicated in psychotomimetic and antipsychotic drug action. In the present study, neurochemical function in the nucleus accumbens and anterior caudate-putamen was examined one week after i.c.v. administration of 1.5, 4.5, or 6.6 nmol of KA. As expected, i.c.v. KA produced dose-dependent neuronal loss in the dorsal and ventral hippocampus. Extrahippocampal neuronal loss was also observed in the thalamus and piriform cortex in some of the KA-treated rats. While ambient levels of dopamine turnover and excitatory amino acids in the nucleus accumbens were unaltered by KA, administration of the highest KA dose elevated [3H]spiperone binding exclusively in the accumbens. Finally, behavioral hyperactivity was observed in KA-treated rats over a five-week period following i.c.v. administration. The pattern of neuronal loss, receptor upregulation, and behavioral hyperactivity found after i.c.v. KA administration may provide a useful animal model of the limbic neuropathology and neurochemical dysfunction associated with schizophrenia.
脑室内（i.c.v.）注射海藻酸（KA）会导致海马体及内侧颞叶其他区域出现不同程度的神经元损失。这些脑区中的许多都向伏隔核发出兴奋性投射，伏隔核是一个与拟精神病药物和抗精神病药物作用有关的多巴胺能脑区。在本研究中，在脑室内注射1.5、4.5或6.6 nmol KA一周后，检测了伏隔核和前尾状核 - 壳核的神经化学功能。正如预期的那样，脑室内注射KA在背侧和腹侧海马体中产生了剂量依赖性的神经元损失。在一些接受KA治疗的大鼠的丘脑和梨状皮质中也观察到了海马体外的神经元损失。虽然伏隔核中多巴胺周转率和兴奋性氨基酸的环境水平未因KA而改变，但最高剂量的KA注射仅使伏隔核中的[3H]司哌罗宁结合增加。最后，在脑室内注射KA后的五周时间里，观察到接受KA治疗的大鼠出现行为多动。脑室内注射KA后发现的神经元损失、受体上调和行为多动模式可能为与精神分裂症相关的边缘神经病理学和神经化学功能障碍提供一个有用的动物模型。
