title: Tacrine and bis(7)-tacrine attenuate cycloheximide-induced amnesia in mice, with attention to acute toxicity.
abstract: Effects of tacrine and bis(7)-tacrine (0.25-20 μmol/kg, s.c.) on cognitive behaviour in cycloheximide (CYH)-treated mice were investigated. Cognitive behaviour was assessed by open-field test and step-through task with a 24-hr retention interval. Drugs or vehicle was given 30 min. prior to the first session. Although CYH treatment (110 mg/kg, i.p.) alone did not affect the locomotor activity of mice, CYH treatment in combination with tacrine (20 μmol/kg) decreased the locomotor activity by 37% in the acquisition session, when compared with mice treated with CYH alone. Bis-(7) tacrine cotreatment did not produce any detectable effect on locomotor activity. During the retention trial, tacrine (5 μmol/kg) or bis(7)-tacrine (1 μmol/kg) enhanced the retention latency (by 3.8- or 1.4-fold, respectively) in CYH-treated mice. In both training and retention trials, CYH treatment increased the number of footshocks (by 50% and 11.3-fold, respectively). However, during the retention (but not training) trial, tacrine (5 μmol/kg) or bis(7)-tacrine (1 μmol/kg) decreased the footshocks (by 8.6-fold or 39%, respectively) in CYH-treated mice. Combined treatment with CYH and bis(7)-tacrine (but not tacrine) resulted in an increased mortality rate in mice. The results indicated that tacrine and bis(7)-tacrine improved the amnesia caused by CYH treatment. However, the combined treatment with bis(7)-tacrine and CYH administration caused acute toxicity.
authors.affiliation: Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China. siyuan-pan@163.com
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Guo
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Han
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003513:Cycloheximide / Q000633:toxicity*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D013619:Tacrine / Q000494:pharmacology*; D023382:Toxicity Tests, Acute
chemical_list: D018697:Nootropic Agents; D011500:Protein Synthesis Inhibitors; D013619:Tacrine; D003513:Cycloheximide