サル前頭前野におけるドーパミンによるグルタミン酸放出の制御

抄録

It has been well documented that the prefrontal cortex (PFC) plays important roles in performance of working memory (WM) tasks. Furthermore, dopamine (DA) and glutamate in the PFC are shown to be indispensable for WM task performance both in the rat and monkey. We previously reported that there was a double dissociation in changes in glutamate and dopamine between a WM (spatial delayed alternation) task and a non-WM (sensory guided control) task i.e., a significant increase in dopamine but no change in glutamate during the WM task and a significant increase in glutamate but no change in dopamine during the sensory guided task. In order to clarify the mechanism of this dissociation, we investigated a DA-glutamate interaction in the PFC in the unanesthetized condition, using reverse dialysis method. As the application of 1 mM dopamine itself(78.87 ± 12.17, p = 0.049, n = 8), the simultaneous application of dopamine D₁ (SKF38393; 1.0 mM) and D₂ (quinelorane; 1.0 mM) receptor agonists significantly decreased glutamate levels in the PFC (85.01 ± 4.33%, p = 0.019, n = 8). On the contrary, neither norepinephrine (1 mM) nor clonidine (α₂ agonist)(0.1 mM, 0.5 mM, 1.0 mM, 2.0 mM) affected glutamate releases significantly. After a solo application of D₂ agonists, glutamate levels decreased in a dose dependent manner. Furthermore, this decrease of glutamate by quinelorane was not antagonized by 0.5 mM muscimol. The results suggest that dopamine D₂ receptors, but not α₂ receptors, have disfacilitatory roles for the WM. [J Physiol Sci. 2006;56 Suppl:S195]