Excitatory neurotransmitters in kindling: excitatory amino acid, cholinergic, and opiate mechanisms.

The role of excitatory neurotransmitters in kindling is selectively reviewed. Evidence from a variety of approaches strongly indicates that muscarinic cholinergic and excitatory amino acid neurotransmission contributes to electrical kindling in the rat. Among the latter group of neurotransmitters, N-m-d-aspartate receptors are known to play a role, but quisqualate and kainate receptors also may play a role. Delta and epsilon opiate receptors appear to be capable of mediating the development of kindled seizures, but their contribution to electrical kindling may be less than that of excitatory amino acid and cholinergic mechanisms. However, none of these systems is critical for kindling since antagonism of any one of them only retards kindling at best, but does not completely block it. Antagonism of both N-m-d-aspartate and muscarinic receptors results in greater retardation of electrical kindling than does antagonism of either receptor type alone, which implicates a mechanism involving the summation of excitatory neurotransmission in kindling. The use of the N-m-d-aspartate receptor antagonist aminophosphonovaleric acid for the pharmacological dissociation of kindling and long-term potentiation indicates that long-term potentiation in the perforant path-dentate circuit is critically dependent upon N-m-d-aspartate neurotransmission, but kindling is not. This suggests that long-term potentiation is not a critical element in the mechanism of kindling in this circuit.