Modification of [3H]MK801 binding to rat brain NMDA receptors after the administration of a convulsant drug and an adenosine analogue: a quantitative autoradiographic study.
Specific [3H]MK801 binding to rat brain NMDA receptors after the administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) was studied by means of a quantitative autoradiographic method. MP administration (150 mg/kg, i.p.) caused significant decreases in [3H]MK801 binding in several hippocampus subareas and layers, mainly in CA1 and CA3 at seizure (11-27%) and postseizure (8-16%) and in cerebral occipital cortex at seizure (18-22%). In nucleus accumbens, a rise was observed at postseizure (44%) and a tendency to increase at seizure (24%). CPA (2mg/kg, i.p.) decreased ligand binding in hippocampus (CAI, CA2, CA3) (17-22%) and in occipital cerebral cortex (18-24%). When CPA was administered 30 minutes before MP (which delayed seizure onset) and rats were sacrificed at seizure, decreases in [3H]MK801 binding in several layers of CA1 and CA3 of hippocampus (11-27%) and in CA1, CA2, CA3 (24-35%) after CPA+MP postseizure, and an increase in CA2 after CPA and CPA+MP postseizure (20-34%), were observed. A drop was found in the occipital subarea (18-24%) after CPA and in the frontal and occipital subarea after CPA+MP postseizure (24-34%) while no changes were observed in any treatment involving the other cerebral cortex regions, thalamic nuclei, caudate putamen and olfactory tubercle. These results show that [3H]MK801 binding changes according to drug treatment and the area being studied, thus indicating a different role in seizure activity.
Giraldez
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Instituto de Biología Celular y de Neurociencia Prof Eduardo De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Girardi
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E
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003292:Convulsants / Q000008:administration & dosage* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014316:Tritium
D003292:Convulsants; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016291:Dizocilpine Maleate; D000241:Adenosine