129. Tacrine treatment at high dose suppresses the recognition memory in juvenile and adult mice with attention to hepatotoxicity

Pan SY[1], Dong H[1], Guo BF[1], Zhang Y[1], Yu Q[2], Ye Y[1,2], Yu ZL[2], Han YF[3], Ko KM[4]

[1] Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China.
[2] School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
[3] Department of Applied Biology & Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China [4] Section of Biochemistry and Cell Biology, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

It is well established that cholinergic over-stimulation can interfere with memory processes. The aim of this study was to evaluate the effect of tacrine, an acetylcholinesterase inhibitor, on recognition memory as well as the associated hepatotoxicity in juvenile (20-day-old) and adult (100-day-old) ICR male mice. Recognition memory was assessed by open-field test and step-through task without footshocks for three sessions between 08:00 and 13:00, with a 24-hr retention interval. Tacrine (10 or 40 lmol ⁄ kg) or vehicle was administered (s.c.) 20 min. prior to the first session. During the acquisition session, tacrine suppressed the open-field behaviours, including locomotor activity, rearing, grooming and defecation (by 77–100%) in mice of both ages. During the recall (observable in both ages) and re-recall (observable in juvenile mice) session, the locomotor activity and rearing number were significantly increased, indicative of impairment in recognition memory, in mice treated with tacrine 40 umol ⁄ kg. During the training trial, tacrine decreased the step-through number in mice of both ages. In contrast, during the retention and re-retention trials, the step-through number was increased (by 92% and 93%, respectively), indicative of impairment in step-through memory, in juvenile but not adult mice treated with tacrine 40 umol ⁄ kg. Tacrine 40 umol ⁄ kg elevated the serum alanine aminotransferase (ALT) activity (by 135%) in juvenile mice, but reduced the ALT activity (by 42%) in adult mice. The results indicated that 20-day-old mice seemed to be more sensitive than 100-day-old mice to tacrine-induced impairment in recognition memory and the associated liver damage