Adenosine receptor antagonists cancelled the ischemic tolerance phenomenonin gerbil

Pretreatment of the brain with sublethal ischemia has been reported to indu ce neuronal resistance to otherwise lethal ischemia, a phenomenon designate d as ischemic tolerance. The protective mechanisms of the phenomenon are no t known yet, however, recent experimental data suggest the involvement of a denosine 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 theophyllin e 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) sig nificantly reduced the protective effect of preconditioning in the CAI hipp ocampal neurons. These findings suggest the involvement of adenosine recept or activation for the development of ischemic tolerance phenomenon. (C) 200 1 Elsevier Science B.V. All rights reserved.