Effects of caffeine on NMDA-evoked 45Ca2+ release in the rat dentate gyrus in vivo
Selected contents from this journal
Languages of publication
Caffeine in 10-2 M concentration per se activates ryanodine receptors (RyR) in vitro, thereby increasing the intracellular concentration of Ca2+ ([Ca2+]i). In general opinion, caffeine applied in vivo in much lower doses does not affect [Ca2+]i in neurones. However, it was recently demonstrated that caffeine in low concentrations in vitro potentiates evoked Ca2+ release in neurones via RyR. Microdialysis of the rat dentate gyrus (DG), combined with measurement of 45Ca2+ efflux, has been used in our laboratory to study in vivo NMDA-evoked calcium induced calcium release (CICR) via RyR. The aim of the present microdialysis study was to investigate in vivo effects of caffeine, applied systemically in a pharmacologically-relevant dose, and locally in the dialysis medium in very high concentration, on the NMDA-evoked CICR in DG neurones. To ensure steady brain concentration of caffeine, its systemic (i.p.) administration in a dose of 40 mg/kg was followed by a continuous i.p. infusion of 80 mg/kg/min and application of 0.4 mM caffeine in the dialysis medium. The results demonstrated that in the rat DG, local administration of 50 mM caffeine significantly stimulates a spontaneous 45Ca2+ efflux and its release induced by 5 mM NMDA. However, systemic administration of caffeine had no effect on spontaneous and NMDA-induced 45Ca2+ release in the rat DG, which supports the view that caffeine, applied in vivo, even in high doses, does not influence CICR in brain neurones.
Publication order reference
J. W. Lazarewicz, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawinski St., 02-106 Warsaw, Poland, Email: firstname.lastname@example.org