Convulsant bicuculline modifies CNS muscarinic receptor affinity

We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg) and convulsant (7.5 mg/kg) doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity.Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process itself. Findings support the notion that the muscarinic receptors play a major role in experimental epilepsy and provide a new example of differential neuronal plasticity.An imbalance between inhibition and excitation in the CNS may lead to seizures that involve the synchronous and repetitive discharges of a large group of neurons.Convulsant drug administration has proven to be effective and therefore a useful tool to study experimental epilepsy, since it produces behavioral modifications concomitant with marked neurochemical changes. Acetylcholine is an essential neurotransmitter/neuromodulator in several experimental epilepsy disorders [1], and its ability to regulate neuronal excitability in neocortex is well known [2]. Interestingly, the anticonvulsant effect mediated by carbachol microinjection in the nucleus reticularis pontis oralis app