Acute peroxide treatment of rat hippocampal slices induces adenosine-mediated inhibition of excitatory transmission in area CA1

Brief exposure to conditions that generate free radicals inhibits synaptic transmission in hippocampal slices, most likely via a presynaptic mechanism. Because other physiologically stressful conditions that generate free radicals, such as hypoxia or ischemia, stimulate the release of adenosine from brain slices, we determined whether increases in extracellular adenosine mediate the presynaptic inhibition of excitatory transmission induced by peroxide treatment. Simultaneous addition of hydrogen peroxide (0.01%) and ferrous sulfate (100 mu M) resulted in a >80% decrease in synaptic potentials recorded in the CA1 region of hippocampal slices of adult male rats. Treatment with theophylline (200 mu M), a non-selective adenosine receptor antagonist, or 8-cyclopentyl-1,3-dipropylxanthine (100 nM), a selective adenosine A(1) receptor antagonist, prior to and during hydrogen peroxide superfusion prevented the inhibition. These results demonstrate that acute exposure to hydrogen peroxide induces an adenosine-mediated decrease in synaptic transmission in hippocampal slices. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.