Abstract
ObjectiveThis research was aimed to evaluate the behaviors of short‐ or long‐term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS).BackgroundKetamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory.MethodsAfter 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43–75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short‐term) or 7 weeks after ketamine treatment (long‐term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety‐like behavior (OF and EPM), forced swimming (FS), and water maze (WM).Results: Short‐term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety‐eliciting situations. No significant differences in these behaviors were obtained under conditions of long‐term ketamine administration (p > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long‐term effects of ketamine (*p < .05). Nor were significant differences obtained in learning and memory performance in rats receiving ketamine (p > .05).ConclusionTaken together these findings demonstrate that a short‐term administration of ketamine induced rapid antidepressant‐like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long‐term treatment regime.
Highlights
Depression is the most common mental disorder in community settings and a major cause of disability worldwide
It has been reported that the prevalence of depression in most countries ranges from 8 to 12%, which results in enormous personal suffering, as well as substantial social and economic burdens (Kessler et al, 2003; Pincus & Pettit, 2001)
The rapid recovery of body weight in stressed rats treated with ketamine suggests that NMDA receptors are involved in modulating feeding behavior during stressful situations
Summary
Depression is the most common mental disorder in community settings and a major cause of disability worldwide. It is generally believed that the increase in neuronal monoamine neurotransmitter transport that occurs in response to these agents can improve the adaptability of neurons in the limbic brain regions that control mood and depression, to achieve their therapeutic effect (Warner-Schmidt et al, 2010) These typically prescribed antidepressants have significant limitations, including low effective rates upon initial use (effective rates to the first treatment account for only one-third, and effective rates with multiple trials accounts for only up to two-t hirds of treated patients), substantial latencies for a therapeutic response (weeks to months) and serious side effect (such as decreased libido and weight increases) (Trivedi et al, 2006). The specific goals of this study were to examine whether ketamine could improve depression-like behaviors seen in rats subjected to CUS, and to determine the rapidity and duration of these antidepressant effects of ketamine
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