Tacrine and Bis(7)-Tacrine Attenuate Cycloheximide-Induced Amnesia in Mice, with Attention to Acute Toxicity

Effects of tacrine and bis(7)-tacrine (0.25-20μmol/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 30min. prior to the first session. Although CYH treatment (110mg/kg, i.p.) alone did not affect the locomotor activity of mice, CYH treatment in combination with tacrine (20μmol/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 (5μmol/kg) or bis(7)-tacrine (1μmol/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 (5μmol/kg) or bis(7)-tacrine (1μmol/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.