Adenosine receptor antagonists cancelled the ischemic tolerance phenomenon in gerbil.

Pretreatment of the brain with sublethal ischemia has been reported to induce neuronal resistance to otherwise lethal ischemia, a phenomenon designated as ischemic tolerance. The protective mechanisms of the phenomenon are not known yet, however, recent experimental data suggest the involvement of adenosine receptor activation in the acquisition of tolerance. In this study, the effect of theophylline, a non-selective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor antagonist, were investigated to ascertain if these drugs could cancel the protective effect of ischemic tolerance in the gerbil. DPCPX or theophylline was administered at 3 h after a short preconditioning ischemia, and 21 h later animals were subjected to lethal ischemia of 5 min duration. DPCPX at a dose of 1.0 mg/kg (i.p) and theophylline at a dose of 20 mg/kg (i.p) significantly reduced the protective effect of preconditioning in the CA1 hippocampal neurons. These findings suggest the involvement of adenosine receptor activation for the development of ischemic tolerance phenomenon.