Evaluation of acute tacrine treatment on passive-avoidance response, open-field behavior, and toxicity in 17- and 30-day-old mice.
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 micro mol/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 micro mol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 micro mol/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 micro mol/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 micro mol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 micro mol/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.
Pan
S Y
SY
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China. siyuan-pan@163.com
Han
Y F
YF
Yu
Z L
ZL
Yang
R
R
Dong
H
H
Ko
K M
KM
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003672:Defecation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013619:Tacrine / Q000633:toxicity*
D013619:Tacrine