Pharmacologic evidence for a tonic muscarinic inhibitory input to the Edinger-Westphal nucleus in the dog

The cholinergic characteristics of the parasympathetic preganglionic cell groups controlling pupillary diameter were investigated. Drugs dissolved in 0.5 μl 0.9% NaCl were microinjected into sites within or near the Edinger-Westphal nucleus (EW) that yielded pupilloconstriction to electrical stimulation in the decerebrate and awake dog. In the awake dog, carbachol (0.3 to 1.4 nmol), bethanechol (0.5 to 5 nmol), and physostigmine (7.5 and 15.4 nmol), but not nicotine (1.3 to 63 nmol), produced a dose-dependent mydriasis. This cholinergic-induced mydriasis was prevented by methylatropine nitrate (2.7 nmol in 1.0 μl) microinjected 30 min before the agonists. Equimolar doses (2.7 nmol) of- the nicotinic antagonists, mecamylamine and hexamethonium, did not block the carbachol-induced mydriasis. Microinjections of methylatropine, but not the nicotinic antagonists, produced miosis. A muscarinic-induced mydriasis appeared to be due to inhibition of the pupilloconstrictor neurons because (i) it occurred in the chronically sympathectomized and acutely decerebrated dog, and (ii) it did not correlate with sympathetic responses.