Ligand binding to CNS muscarinic receptor is transiently modified by convulsant 3-mercaptopropionic acid administration

The administration of convulsant drugs has proven a powerful tool to study experimental epilepsy. We have already reported that the administration of convulsant 3-mercaptopropionic acid (mp) at 150 mg/kg enhances binding affi nity of muscarinic antagonist [H-3]quinuclidinyl benzilate ([H-3]QNB) to ce rtain rat CNS membranes during seizure and postseizure without affecting si te number. Results obtained with a 100-mg/kg dose of mp have shown reversib le increases in [H-3]QNB binding to cerebellum and hippocampus, whereas a d elayed response has been found in striatum. Neither a subconvulsant dose no r in vitro addition modifies binding. In order to evaluate preseizure, seiz ure as well as early (30 min) and late (24 h) postseizure stages, we employ ed a 50 mg/kg dose and tested [H-3]QNB binding to CNS membranes. Changes in binding were as follows (in %): in cerebellum, +37, +86, and +40 at presei zure, seizure and early postseizure stages, respectively, but there was a d ecrease at late postseizure; in hippocampus, +27 at pre- and seizure stages , but a decrease at early and late postseizure. No changes were found in st riatum or cerebral cortex membranes at any stage studied. Saturation curves analysed by Scatchard plots indicated that changes in [H-3]QNB binding to cerebellar membranes are attributable to an increase in ligand affinity at seizure, followed by a decrease in binding site number at postseizure. A si milar profile was observed for hippocampus except that the decrease in bind ing site number, though lower than at postseizure, was already evident at s eizure stage. Results confirm a region-specific response to the convulsant and transient changes provide an example of neuronal plasticity.