title: Tacrine treatment at high dose suppresses the recognition memory in juvenile and adult mice with attention to hepatotoxicity.
abstract: 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 μmol/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 μmol/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 μmol/kg. Tacrine 40 μmol/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.
authors.affiliation: Department of Pharmacology, Beijing University of Chinese Medicine, China. siyuan-pan@163.com
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
authors.forename: Hang
authors.initials: H
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Han
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D021641:Recognition, Psychology / Q000187:drug effects*; D012153:Retention, Psychology / Q000187:drug effects; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D013619:Tacrine; D000410:Alanine Transaminase