OPPOSITE MODULATION OF 4-AMINOPYRIDINE AND HYPOXIC HYPEREXCITABILITY BY A1 AND A2 ADENOSINE RECEPTOR LIGANDS IN RAT HIPPOCAMPAL SLICES

The effects of the adenosine receptor antagonist 1,3-dipropyl-8-cyclop entylxanthine (DPCPX), and of the adenosine agonists N-6-cyclopentylad enosine (CPA), N-6-(2-phyenylisopropyl)adenosine (R-PIA), and yl)pheny lethylamino]5'-N-ethylcarboxamidoadenosine (CGS 21680 were investigate d on the hyperexcitability induced in the CA1 area of rat hippocampal slices by hypoxia or the epileptogenic agent 4-aminopiridine. Slice pe rfusion with the mixed adenosine receptor agonist R-PIA (0.2 mu M) sig nificantly (P < 0.05) decreased: (i) the number of slices showing a tr ansient CA1 epileptiform bursting during the hypoxic period; (ii) the duration of the hypoxia-induced epileptiform bursting. Conversely, sli ce perfusion with the selective A1 adenosine receptor antagonists DPCP X (0.2 mu M) or with the selective A2 adenosine receptor agonist CGS 2 1580 significantly (P < 0.05) increased the number of slices showing a transient CA1 epileptiform bursting during the reoxygenation period, while the other drugs failed to affect it. Slice perfusion with the se lective A1 adenosine receptor agonist CPA (2 mu M or R-PIA (5 mu M) si gnificantly (P < 0.05) decreased the duration of the CA1 epileptiform bursting induced by the 100 mu M 4-aminopyridine. CGS 21680 (5 mu M) p erfused together with CPA (2 mu M) significantly (P < 0.05) counteract ed the inhibitory effects of the A1 adenosine receptor agonist on 4-am inopyridine epileptiform bursting, while it failed by itself to direct ly affect the 4-aminopyridine epileptiform bursting duration. Ther res ults produce evidence for a selective opposite modulation by A1 and A2 adenosine agonists in the control of hippocampal hyperexcitability in duced by hypoxia or 4-aminopyridine but not in the post-hypoxic functi onal recovery.