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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2006-09, Vol.85 (1), p.50-56
• Main Authors: Pan, S.Y., Han, Y.F., Yu, Z.L., Yang, R., Dong, H., Ko, K.M.
• Format: Article
• Language: English
• Subjects: Acute toxicity; Animals; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Biological and medical sciences; Defecation; Defecation - drug effects; Developmental changes; Drug Evaluation, Preclinical; Hepatotoxicity; Liver - drug effects; Locomotor; Male; Medical sciences; Mice; Mice, Inbred ICR; Neuropharmacology; Open-field memory; Passive-avoidance response; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Tacrine; Tacrine - toxicity
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2006.07.006

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 IC 50 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 IC 50 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.