81. Evaluation of acute tacrine treatment on passive-avoidance response, open-field behavior, and toxicity in 17-and 30-day-old mice

PAN S. Y. ⁽¹⁾ ; HAN Y. F. ⁽²⁾ ; YU Z. L. ⁽³⁾ ; YANG R. ⁽¹⁾ ; DONG H. ⁽¹⁾ ; KO K. M. ⁽²⁾ ;

⁽¹⁾Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, CHINA
⁽²⁾ Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, HONG-KONG
⁽³⁾ School of Chinese Medicine Hong Kong Baptist University, Kowloon Tong, HONG-KONG

The potential of tacrine in altering cognitive/behavioral function as well as in causing toxicity was evaluated in mice of 17 and 30 days of age. Cognitive and behavioral studies were performed using a step-through passive avoidance task and a habituation open-field test with a 24-h retention interval. Tacrine was subcutaneously injected (1.25-80 μmol/kg) 30 min prior to the first session of both tests. During the training session in step-through task, tacrine treatment dose-dependently decreased the number of footshocks, with IC₅₀ values being 7.8 and 23.3 μmol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 μmol/kg) significantly prolonged the retention latency in 17-day-old mice only, but it shortened the retention latency at high doses of 20 and 40 μmol/kg in 17- and 30-day-old, respectively. During the acquisition session in the open-field test, tacrine treatment dose-dependently decreased the locomotor activity in 17- and 30-day-old mice, with IC₅₀ values being 15.1 and 24.7 μmol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 μmol/kg caused a significant increase in serum alanine aminotransferase activity in 17- and 30-day-old mice at 6 h post-dosing, with the extent of stimulation in 30-day-old mice being more prominent. In conclusion, tacrine was more potent in enhancing/disrupting the cognitive function, inhibiting locomotor activity as well as in causing hepatotoxicity in 17-day-old than in 30-day-old mice.