Involvement of muscarinic receptor on the impairment of avoidance learningin mice fed a thiamine-deficient diet

Thiamine-deficient (TD) mice showed a significant decrease in step-through latency time on the 15th and 20th day after TD feeding, as measured by a pa ssive avoidance task. A single injection of thiamine HCl (50 mg/kg, s.c.) o n the 10th day after TD feeding improved the latency time to the level of t he pair-fed control group. Moreover, we investigated the effect of choliner gic drugs on the impairment of avoidance learning in TD mice. The drugs cho sen were the non-selective muscarinic agonist oxotremorine, the nicotinic a gonist lobeline, the selective muscarinic agonist oxotremorine, the nicotin ic agonist lobeline, the selective muscarinic M1 agonist McN-A-343 and the selective muscarinic M2 antagonist methoctramine. The impairment of avoidan ce learning on the 20th day was improved by administration of oxotremorine (0.1 mg/kg, i.p.) or McN-A-343 (20 mug/mouse, i.c.v.). In contrast, adminis tration of lobeline (0.625-10 mg/kg, i.p.) or methoctramine (2.25 - 9 mug/m ouse, i.c.v) did not have an effect on TD induced impairment of avoidance l earning. These results suggested that the muscarinic M1 receptor may be inv olved in the impairment of avoidance learning induced by TD.