Cholinergic therapy of abnormal open-field behavior in thiamin-deficient rats

Although thiamin deficiency is associated with impaired acetylcholine metabolism, the functional significance of the cholinergic lesion is controversial. Therefore, we tested the effect of cholinergic drugs on abnormal open-field behaviors in rats that were treated with a thiamin-deficient diet and thiamin antagonist. After only 1 day of treatment, staring increased significantly in rats given pyrithiamin, a centrally acting thiamine antagonist, but not in rats given oxythiamin, which acts only peripherally. Sniffing, resting and grooming were not altered by either treatment. The acetylcholinesterase inhibitor physostigmine was as effective as thiamin in decreasing staring in pyrithiamin-treated rats, but its peripherally acting analogue neostigmine had no effect. The central muscarinic blocker, atropine, blocked the effect of physostigmine. Methatropine, which acts only peripherally, did not. Arecoline, a direct muscarinic agonist, was as effective as physostigmine in decreasing staring. Nicotine had no effect, and the nicotinic ganglionic blocker mecamylamine did not block the effect of physostigmine. Increased staring behavior in pyrithiamin-treated rats appears to reflect an early central cholinergic muscarinic deficit.