The triggering of spreading depression in the chick retina by nicotinic receptor agonists

Spreading depression was evoked in vitro in retinas of 3-6 day old chickens by the nicotinic cholinergic agonists nicotine and cytisine. The response was reproducible and inhibited by the nicotinic cholinergic receptor antagonist mecamylamine and by the NMDA receptor antagonist -3-(2 carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). The response to nicotinic agonists was not inhibited by alpha-bungarotoxin. The data show that spreading depression can be evoked in the chick retina by alpha-bungarotoxin insensitive nicotinic acetylcholine receptor subtypes and that the response is dependent upon NMDA receptor activation. This nicotine evoked spreading depression was inhibited by cadmium chloride indicating the involvement of voltage sensitive calcium channels. It is therefore argued that nicotine evokes spreading depression indirectly, as a result of calcium sensitive glutamate release. The glutamate released thus exerting its effects via NMDA receptors.