シクロスポリンは前頭前野におけるドーパミンとセロトニンの放出を減少させる

抄録

Cyclosporine is widely used in immunosuppressive therapy for organ transplantation and autoimmune disease. However, cyclosporine administration causes neuropsychological side effects such as depression, anxiety, confusion, and tremor in some patients. We have previously shown that cyclosporine induces anxiety-related behaviour and decreases social behaviour in mice, and that clozapine partially restored social behaviour in cyclosporine-injected mice. The prefrontal cortex has been shown to control anxiety-related and social behaviour. In the present study, we examined effects of cyclosporine and clozapine upon release of dopamine and serotonin within the prefrontal cortex. Microdialysis probes were inserted in the prefrontal cortex of urethane anaesthetized mice, and contents of dopamine and serotonin in the perfusates were measured by HPLC with electrochemical detection. Release of dopamine and serotonin was reduced in the cyclosporine-treated mice. In the mice that received both cyclosporine and clozapine, dopamine release was not reduced. All these data are consistent with the hypothesis that cyclosporine disturbs social behaviour as a result of reduced dopamine release in the prefrontal cortex. [J Physiol Sci. 2007;57 Suppl:S135]