The Effects of Repeated Ketamine Administration During Adolescence on Anxiety and Depressive-like Behaviors Induced by a Predator Odor
Disorders of anxiety and depression are major public health problems evident by their increasing prevalence and lack of effective treatments. These disorders are highly comorbid and share several debilitating symptoms. Previous research has implicated ketamine in the treatment of depression because of its rapid effects. Ketamine is a noncompetitive NMDA receptor antagonist that stimulates glutamate transmission. The efficacy of non-competitive NMDA receptor antagonists in anxiety treatment, however, lacks consistent findings. The goal of the present study was to examine the effects of repeated ketamine administration during rat adolescence on anxiety and depressive-like behaviors induced by a predator odor. The use of animal models of anxiety is essential to understanding the neuropathology of anxiety and depression and developing new drug treatments. A common non-invasive animal model of anxiety involves exposing the animal to the odor of a natural predator. Ketamine was administered from PND 45-51, which is considered a conservative age range for adolescence (Spear, 2000). On PND 65, half of the rats were exposed to the odor of a domestic cat, which was presented via cat collars and hand towels attached to the home cage. All animals were then subjected to the sucrose preference test (SPT) and the elevated zero maze (EZM) in order to measure the presence of depressive and anxiety-like behaviors, respectively. There was a drug x odor interaction effect trending toward significance in the habitation phase of the SPT, indicating that the ketamine reversed the reduction in sucrose preference due to the predator odor. There were no significant results from the test phase of the SPT. The elevated zero maze was conducted on two consecutive days. Results for day 2 of EZM testing revealed a significant main effect of odor indicating that the rats exposed to the predator odor made significantly fewer entries into the open quadrants compared to the rats exposed to the control odor. The results demonstrate that ketamine only influenced depressive-like behaviors, thus indicating dissociation between the drug’s effect on models of depression and anxiety. Overall, the results provide some support for the preventative effects of ketamine on depressive-like behaviors.
anxiety, depression, ketamine, predator odor, sucrose preference test, elevated zero maze, Social and Behavioral Sciences
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