Effect of dantrolene on K(+)- and caffeine-induced dopamine release in rat striatum assessed by in vivo microdialysis.

Recently, dantrolene has been reported to affect the central nervous system in addition to peripheral targets such as skeletal muscle. We examined effects of dantrolene on K(+)- and caffeine-induced dopamine release in rat striatum using in vivo microdialysis. Perfusion with KCl via the dialysis probe for 20 min induced immediate increase in DA release. Either chelation of extracellular calcium or addition of dantrolene for 120 min preceded reapplication of 100 mM KCl for 20 min. Calcium chelation attenuated the increase in DA release induced by KCl. Application of dantrolene enhanced the KCl-induced increase in DA release, but this effect disappeared at 100 microM. Caffeine caused a dose-dependent increase in dopamine release, independently of extracellular calcium. Treatment with 100 microM dantrolene for 120 min reduced the increase in DA release induced by caffeine. These findings that dantrolene modulates dopamine release in rat striatum indicate that conventionally administered dantrolene is likely to act on the central nervous system.