Behavioral pharmacological and molecular biological study on the emotional symptoms of schizophrenia for the pathogenesis of psychiatric disorders. ---The relationship between aggression/anxiety and excitatory amino acid in the chronic

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The purpose of this study is to clarify the effect of chronic methamphetamine treatment on aggressive behavior and anxiety and to examine the functional role of various brain regions for aggression and anxiety and the relationship between glutamate neurotransmission and emotional behavior.1) Repeated methamphetamine treatment increased aggressive behavior and anxiety, which was antagonized by the pretreatment with the dopamine2 receptor antagonist as shown in our previous study.2) MS-153, an inhibitor for glutamate release, inhibited both the acquisition and expression of conditioned freezing, an index of anxiety/fear. Repeated MS-153 pretreatment enhanced the inhibitory effect of MS-153 on the acquisition of conditioned fear. These indicate that endogenous glutamate is related to the acquisition and expression of anxiety or fear.3) The radiofrequency lesions of the amygdala and the mediodorsal nuleus of the thalamus inhibited both the acquisition and expression of conditioned fear. These results suggest that both brain regions play an important role for the development and expression of anxiety.4) Chronic treatment with staurosporine, a protein kinase C inhibitor, reduced the acquisition, but not expression, of conditioned fear.