THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL ThzaA.pEu’rlcs Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics Impairment of Behavior and Acetyicholine Metabolism in

After only 1 day of treatment with a thiamine-deficient diet and pyrithiamine, a centrally and peripherally acting thiamine an-tagonist, 37.5 % of rats performed poorly on a standardized string test. By day 1 2, 89.6 % of the pyrithiamine-treated rats, but only 8. 1 % of the pair-fed controls, had decreased string test scores. Scores for rats treated with a thiamine-deficient diet and oxythiamine, a peripherally acting thiamine antagonist, did not decrease even on the day before death. The acetylcho-linesterase inhibitor physostigmine improved the low string test scores in 69.2 % of trials with the pyrithiamine-treated rats, whereas neostigmine, which acts peripherally, had no effect. The effect of physostigmine was inhibited by the muscarinic blocker atropine, but not by methatropine, its peripherally acting analog. Arecoline, a direct muscarinic agonist, was as effective as physostigmine or thiamine in restoring string tes