Abstract

STUDY OF DOSE RESPONSE CHARACTERISTICS OF SUBANAESTHETIC DOSES OF KETAMINE ON COGNITIVE FUNCTION AND ANXIETY BEHAVIOUR IN RATS

Abstract

Objectives: Ketamine, a Schedule III drug under the Controlled Substances Act, is a dissociative anaesthetic having combination of stimulant, depressant, hallucinogenic, and analgesic properties. The main objective of this study was to assess the dose-response characteristics of subanaesthetic doses of ketamine on cognitive function and anxiety behaviour in rats. Methods: After overnight fasting, Wistar albino rats were subjected to habituation on T maze, forced alternation training and discrete, paired-trials delayed alternation task: each trial-pair consisted of a forced trial and a choice trial. Upon reaching a stable performance level, the animals randomly received a normal saline or ketamine injection (s.c.) 10 min (8mg/kg) and 25 min (12mg/kg) prior to testing. Anxiety analysis was done using elevated plus maze assessing total time spent in the closed arms and open arm, entries into the open and closed arms and number of head dipping. Results: Ketamine at the dose of 8 mg/kg and 12 mg/kg significantly increased the number of errors (2.8±0.9 and 4.6±0.3) on T maze (p<0.001) significantly reducing the percentage of correct responses compared to control (1±0.3). Also, number of entries in open arm and average time spent in open arm and number of head dipping by rats treated with ketamine were significantly higher compared to control (p<0.001). The mechanism by which it produces adverse behavioural effects, partly have been attributed to blockade of NMDA receptors located on inhibitory GABAergic neurons. Conclusion: Ketamine in subanaesthetic doses impaired working memory deficit assessed by discrete-trial delayed alternation test and showed possible anxiolytic property.

Keywords: Ketamine, cognitive function, anxiety behaviour, NMDA receptors, GABAergic neurons.