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Research Paper | Medicine Science | United Kingdom | Volume 9 Issue 6, June 2020

Examination of Cognitive Deficits Produced by Sub-Chronic Ketamine Exposure in Rats

Christopher Wood ^[2] | Mohammed Shoib

Abstract: Chronic NMDA receptor suppression by NMDA antagonists (ketamine), induce structural changes in neocortical and limbic brain regions, resulting in similar cognitive deficits to that observed clinically in schizophrenia. Objectives: This study was designed to evaluate cognitive deficits following ketamine administration in rodents, assessed through an attentional set-shifting paradigm. Thus, allowing evaluation of cognitive flexibility in the form of discrimination acquisition, reversal learning and intra/extra-dimensional shifts (ability to switch between dimensions). Methods: Forty four male Lister Hooded rats, underwent a five day daily sub-chronic treatment regime prior to habituation. The three treatment groups where; VEH, ketamine (10mg/kg, IP) and ketamine (30mg/kg, IP). Rats underwent habituation two days post treatment cessation, consisting of a simple odour and medium discrimination.24 Hours later, rats were assessed on a attentional set shifting task. Results: Sub-chronic ketamine treatment impaired reversal learning in a dose dependent manner. Animals treated with ketamine (30mg/kg), required significantly more trials to criterion for all three reversal trials (REV1-3). Ketamine (10mg/kg) treatment significantly impaired acquisition during REV2. Ketamine (30mg/kg) treated rats made significantly more errors during each reversal (REV1-3). A clear trend emerged between ketamine exposure and latency; rats treated with ketamine (30mg/kg) required longer to complete REV1 to EDS. Ketamine (30mg/kg) treatment resulted in a significant deficit in the acquisition of the odour and medium tasks, during habituation. Conclusion: These results show sub-chronic ketamine treatment impairs reversal learning. Our findings support the impairments observed clinically following CANTAB assessment in schizophrenic patients. Hence, our data suggests sub-chronic ketamine treatment results in similar cognitive deficits. Our results support the hypothesis that ketamine is an important pharmacological compound to model cognitive deficits in rats.

Keywords: Schizophrenia, Chronic Ketamine, Set-shifting, Rat

Edition: Volume 9 Issue 6, June 2020,

Pages: 1893 - 1903

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