Control of 4-aminopyridine-induced synchronous activity by adenosine A1 and mu-opioid receptor agonists in adult rat hippocampus.
In the presence of 4-aminopyridine (4AP, 50 microM) two types of spontaneous field potentials can be recorded in the CA3 stratum radiatum of adult rat hippocampal slices. First, epileptiform interictal discharges (0.85 +/- 0.25 Hz) that are blocked by excitatory amino acid ionotropic receptor antagonists. Second, negative-going synchronous potentials (0.036 +/- 0.015 Hz) which are solely abolished by application of bicuculline methiodide (BMI). Bath application of the specific adenosine A1 receptor agonist, N6-(L-2-phenylisopropyl) adenosine (L-PIA), reduced the frequency of interictal discharges in a dose-dependent manner (IC50 = 8.75 microM; n = 9 slices) and this effect was reversed by the specific adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 microM; n = 3 slices). L-PIA did not affect the frequency of occurrence of the negative-going field potential during application of excitatory amino acid receptor antagonists. This BMI-sensitive event was depressed, however, by application of the mu-opioid receptor agonist [D-Ala2-N-Me-Phe4,Gly5(5)-ol]enkephalin (DAGO, 10 microM; 15.1 +/- 8.7% of rate in control; n = 6 slices), an effect that was antagonized by naloxone (20 microM). Our results indicate that L-PIA reduces the 4AP-induced epileptiform activity through the activation of adenosine A1 receptors. This procedure does not influence the BMI-sensitive field potential, which is abolished, however, by DAGO. Thus, our findings support the hypothesis that the BMI-sensitive potential is due to the presynaptic release of GABA from interneurons.
Barbarosie
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MT
Montreal Neurological Institute, McGill University, Que., Canada.
Nagao
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Avoli
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D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*
D004745:Enkephalins; D058906:Purinergic P1 Receptor Agonists; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C017069:bicuculline methiodide; D015761:4-Aminopyridine; D001640:Bicuculline