Abstract:

Objective   To explore effects of long-term low-dose ketamine treatment on locomotor activity and apoptosis of the thalamus in cynomolgus monkeys.  Methods   12 male cynomolgus monkeys ［(46.25±5.40)months old］ were randomly divided into the ketamine group(n=8) and the control group(n=4). Monkeys in the ketamine group were injected with 1mg/mL of ketamine,1mL/kg; while those in the control group were injected with an equal dose of normal saline(1mL/kg). Locomotor activities of all monkeys were recorded at regular intervals. 3 months later, monkeys were sacrificed. The apoptosis of thalamic cells was observed by TUNEL staining. Western blot was used to detect Caspase-3 and Bcl-2 expressions.  Results   There was no statistically significant difference in locomotor activity between the ketamine group and the control group. The ketamine group showed a statistically significant decrease in locomotor activity with prolongation of treatment time, while the control group had no statistically significant change. The ketamine group showed a statistically significant increase in apoptosis and the Caspase-3 level in the thalamus compared with the control group. There was no statistically significant difference in the Bcl-2 expression between the two groups.  Conclusion   Chronic repeated treatment of ketamine with recreational dosage decreases locomotor activities which maybe caused by drug tolerance, and  induces apoptosis of the thalamus which may be associated with up-regulation of Caspase-3.

Key words: Ketamine; Cynomolgus monkeys; Locomotor activity; Apoptosis; Early adult