Abstract:

Objective    To explore effects of long-term low-dose ketamine on behavior and ultrastructures of the hippocampus and prefrontal cortex in Cynomolgus monkeys.  Methods    12 male Cynomolgus monkeys were randomly divided into the ketamine group (n=8) and the control group (n=4). The ketamine group was daily intravenously injected with ketamine(1mg/kg), while the control group injected with normal saline(1mL/kg).  Observations on behavior were regularly made and ultrastructural changes of the hippocampus and prefrontal cortex were observed by a transmission electron microscope after 6 months. Results    There was no statistically significant difference in locomotor activities between the two groups（P﹥0.05）.Ultrastructural changes in the ketamine group, including neuron necrosis, glial cell apoptosis and lipofuscin accumulation, appeared in the hippocampus; a mass of autophagosomes, reduction of the rough endoplasmic reticulum, neuron necrosis, and glial cell apoptosis were observed in the prefrontal cortex in the ketamine group, while not observed in the control group. Conclusion     Long-term low-dose ketamine induces ultrastructural changes in the hippocampus and prefrontal cortex, including neuron degeneration, necrosis and apoptosis, which appear earlier than behavioral changes do.

Key words: Ketamine; Cynomolgus monkey; Behavior; Ultrastructure; Cell death