Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices

Abstract

The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N-methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short-(5–10 min) lasting hypoxic period was significantly increased (P<0.01) by slice perfusion with caffeine (50 μM), DPCPX (0.2 μM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P<0.01) by slice perfusion with L-PIA (0.2 μM) and CPA (0.05 μM). It was not significantly modified by CGS 21680 (5 μM). The incidence of reappearance of the CA1 PS during reoxygenation after long-(45 min) lasting hypoxia was significantly increased (P<0.05) by slice perfusion with MK 801 (50 μM), while it was not significanly affected by slice perfusion with caffeine (50 μM) or DPCPX (0.2 μM) or L-PIA (0.2 μM) or CPA (0.05 μM) or CGS 21680 (5 μM). The results indicate a prevalent involvement of the A 1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period.