Effects of caffeine on NMDA-evoked 45Ca2+ release in the rat dentate gyrus in vivo

• Authors: M. Alaraj , I. Kosinska , J.W. Lazarewicz

Abstracts

EN

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.

Keywords

EN

CAFFEINE; DENTATE GYRUS; MICRODIALYSIS; RAT; RYANODINE

Discipline

• EXPERIMENTAL_BIOLOGY_&_MEDICINE: EXPERIMENTAL BIOLOGY & MEDICINE

• Publisher: Marceli Nencki Institute of Experimental Biology, Polish Academy of Sciences
• Journal: Acta Neurobiologiae Experimentalis
• Year: 1998
• Volume: 58
• Issue: 4
• Pages: 239-246

Contributors

author

M. Alaraj

author

I. Kosinska

author

J.W. Lazarewicz

• Publication order reference: J. W. Lazarewicz, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawinski St., 02-106 Warsaw, Poland, Email: [e-mail]