CHOLINERGIC THERAPY OF ABNORMAL OPEN-FIELD BEHAVIOR IN THIAMIN-DEFICIENT RATS

Although thiamine deficiency is associated with impaired acetylcholine metabolism, the functional significance of the cholinergic lesion is controversial. The effect of cholinergic drugs on abnormal open-field behaviors in rats treated with a thiamine-deficient diet and thiamine antagonists was tested. After only 1 day of treatment, staring increased significantly in rats given pyrithiamine, a centrally acting thiamine antagonist, but not in rats given oxythiamine, which acts only peripherally. Sniffing, resting and grooming were not altered by either treatment. The acetylcholinesterase inhibitor physostigmine was as effective as thiamine in decreasing staring in pyrithiamine-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 pyrithiamine-treated rats appears to reflect an early central cholinergic muscarcinic deficit.