Effects On Locomotor Activity And Apoptosis Of Thalamus Cells Caused By Long-term Ketamine Treatment In Early Adult Cynomolgus Monkeys

Objective To investigate the effects on apoptosis of thalamus and locomotor activity caused by long-term ketamine treatment in cynomolgus monkeysMethods12male cynomolgus monkeys which were(46.25±5.40)months old were randomized to ketamine group and control group.There were8monkeys in ketamine group and4monkeys in control group. The monkeys of ketamine group were injected with lmg/kg ketamine of lmg/mL concentration which were made up in advance. The monkeys of control group were injected with equal NS(1mL/kg). The locomotor activities of all monkeys were recorded by camera at the first day、the30day and the90day.3months later, the monkeys were sacrificed. Three monkeys of ketamine group and one of control group were selected randomly. Those monkeys were flooded with4%polyphosphate formaldehyde solution and the thalamus organization of those monkeys were took out into4%polyphosphate formaldehyde solution for48hours. The apoptosis of thalamus cells of those four monkeys were observed by TUNEL staining. Other8monkeys were flooded with NS and the thalamus organization were took out and preserved in liquidnitrogen for Western bloting. Western blot method was used to detect Caspase-3and Bcl-2expression.Results1.Locomotor activities:There were no significant differences of locomotor activities between ketamine group and control group at the beginning. As time went on, the ketamine group showed increase in locomotor activities gradually and there were statistically significant increase on the90days. This suggest the locomotor activities were inhibited.2. TUNEL:Apoptosis of thalamusstatisticallysignificantly increased compared with the control group and intercellular substance of ketamine group become loose.3. Western Blot:The ketamine group showed statistical significant increase in Caspase-3level. The level of Bcl-2reduced but with no statistical significance.Conclusion1.Long-term low-dose administration of ketamine decreaseslocomotor activities with decline trend which may be caused by drug tolerance.2. Long-term low-dose administration of ketamine induces apoptosis of thalamus which may be associated with up-regulation of caspase-3.