Seizures down-regulate muscarinic cholinergic receptors in hippocampal formation.

Muscarinic cholinergic receptors (MCR) have been previously shown to decline in the hippocampal formation (HPF) of amygdala-kindled rats. Seizures have been proposed as the process responsible for this down-regulation. We now demonstrate similar down-regulation of MCR within HPF in 3 additional methods of inducing seizures: electroconvulsive shock, entorhinal kindling and entorhinal lesion. Two key parameters which causally link the MCR declines with seizures are their time course and reversal with anticonvulsants. The transient decline of MCR induced by entorhinal lesion-induced seizures parallels the time course established in amygdala kindling. Further, phenobarbital could block both these seizures and the MCR declines. Together, this supports the relationship of seizures causing the declines. We postulate that the MCR down-regulation represents an endogenous inhibitory response of neurons that are intensely and repeatedly depolarized during the seizures.