Abstract
Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a dissociative anesthetic, presently included in the category of the psychoactive substances known as “club drugs”. Ketamine administration was associated with impaired working memory and increased psychopathological symptoms, but there is a lack of information regarding the effects of chronic sub-anesthetic doses. Adult Wistar rats were administered ketamine, 5 and 10 mg/kg twice daily, subcutaneously for 14 days. One week later, rats were tested in an object recognition/object location task and in the open field arena. There was altered performance in both the object recognition/location and in the open field tests by the group chronically exposed to the lower dose of ketamine. These animals displayed a decreased discrimination index (p<0.05) in the object recognition task, were unable to recognize the displacement of a familiar object and displayed decreased activity across open filed sessions. Importantly, these alterations were not observed in animals administered a higher dose of ketamine. Collectively, these results consistently show that chronic administration of ketamine in sub-anesthetic doses may lead to decreased habituation and inability to update spatial representations.
Highlights
Ketamine is a clinically and veterinary important drug commonly used in anesthesia and perioperative analgesia [1, 2]
The role of ketamine, as a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in blocking the processing of nociceptive inputs has led to its use in chronic pain syndromes management [4, 5]
Acute subanesthetic doses of ketamine were shown to induce a marked increase in glutamate release in the nucleus accumbens facilitating synaptic flow of information from the prefrontal cortex (PFC) and amygdala [8], which is consistent with the hypothesis that ketamine acts preferentially to block NMDA receptors on inhibitory neurons leading to a state of disinhibition and increased glutamate release in the PFC and limbic regions [8, 9]
Summary
Ketamine is a clinically and veterinary important drug commonly used in anesthesia and perioperative analgesia [1, 2]. The role of ketamine, as a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in blocking the processing of nociceptive inputs has led to its use in chronic pain syndromes management [4, 5]. Ketamine use, both in preclinical studies [6] or in compulsive users was reported to induce cognitive impairments [7]. The administration of chronic and sub-chronic doses of other NMDA antagonists lead to disruption of the hippocampal and PFC function [10,11,12], chronic NMDA-antagonism, has been reported to induce persistent deficits in working memory [10, 13, 14]
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