Behavioral and neurochemical studies on an animal model of schizophrenia.

反复服用甲基苯丙胺会导致人类精神分裂症样精神病和动物行为致敏。对行为致敏的理解可能为甲基苯丙胺诱导的精神病和精神分裂症的发病机制提供见解。已知NMDA拮抗剂阻断致敏的发展，提示谷氨酸在该现象中的作用。在我们之前的项目中，我们发现东莨菪碱，一种毒蕈碱胆碱能受体的拮抗剂，可以阻止行为致敏。因此，中枢胆碱能受体似乎在行为致敏的发展中起作用。在本研究中，我们发现氯硝西泮，一种中枢gaba -苯二氮卓受体的激动剂，可以阻断行为致敏。氟马西尼，一种gaba -苯二氮卓受体拮抗剂，逆转了这种阻断。这些结果表明中枢GABA神经传递参与了这一现象的发生。这些结果可能表明，行为致敏与其他神经可塑性变化（如学习和记忆）具有一些共同的特性。

Repeated administration of methamphetamine results in schizophrenia-like psychosis in human and behavioral sensitization in animals. Understanding of behavioral sensitization may provide insight into the pathogenesis of both methamphetamine-induced psychosis and schizophrenia.It has been known that NMDA antagonists block the development of sensitization, suggesting a role of glutamete in the phenomenon. In our previous project, we found that scopolamine, an antagonist of muscarinic cholinergic receptors, prevented behavioral sensitization. Therefore, central cholinergic receptors seem to play a role in the development of behavioral sensitization. In the present study, we showed that clonazepam, an agonist of central GABA-benzodiazepine receptors, blocked behavioral sensitization. Flumazenil, an antagonist of GABA-benzodiazepine receptors, reversed this blockade. These results suggest that central GABA neurotransmission is involved in the development of the phenomenon.These results may indicate that behavioral sensitization have some common properties with other neural plastic change such as learning and memory.