Influence of adenosinergic drugs on the epileptiform and neurotoxic effects of N-methyl-d-aspartate: comparison with the effects of MK801.
In the present paper, the influence of the adenosine receptor agonist N6-(l-2-phenylisopropyl)adenosine (L-PIA) and of the adenosine receptor antagonist caffeine on the epileptiform and neurotoxic effects of N-methyl-d-aspartate (NMDA) has been tested in rat hippocampal slices. Slice superfusion with 1 microM NMDA changed within 30 min the control CA1 field potentials into an epileptiform bursting in all experiments. Slice superfusion with 0.5-1 microM L-PIA or 50-100 microM caffeine plus 1 microM NMDA inhibited or potentiated, respectively, the CA1 epileptiform bursting duration with respect to a slice superfusion with 1 microM NMDA alone. Slice superfusion with 50-100 microM NMDA induced within a few minutes the appearance of short-lived (1-2 min) additional epileptiform population spikes, followed by an irreversible disappearance of the CA1 population spike. Slice superfusion with 50 microM of the NMDA antagonist dizocilpine (MK801) plus 50-100 microM NMDA prevented in all experiments the irreversible disappearance of the CA1 population spike with respect to a slice superfusion with 50-100 microM alone. Neither in a slice superfusion with 0.5-1 microM L-PIA plus 50-100 microM NMDA nor in a slice superfusion with 50-100 microM caffeine plus 50-100 microM NMDA did this effect occur. The results demonstrate that adenosine receptor ligands modulate the epileptiform but not the neurotoxic effects of NMDA.
Frank
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Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
Scotti de Carolis
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A
Sagratella
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D010660:Phenylisopropyladenosine; D002110:Caffeine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate