Pan SY, Zhang Y, Guo BF, Han YF, Ko KM
 Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China.
 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong SAR, China.
 Division of Life Science, Hong Kong University of Science and Technology, Hong Kong SAR, China.
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.