Neurobehavioural Effects of Acute and Repeated Administrations of Sub-Psychotomimetic Dose of Ketamine in Mice

Abstract

Recent studies have shown that sub-anaesthetic doses of ketamine may induce analgesia, but its psychotomimetic side effects have called for caution. This study therefore, explored a possible sub-psychotomimetic dose of ketamine (SPDK) and determined the influence of frequency of exposure on its neurobehavioural effects in mice. Mice of either sex weighing 18 - 25 g were randomly selected into three major groups: A, B, and C. Group A was distributed into seven sub-groups (n=12) and treated with saline (10 μL/g/body weight); 1, 2, 4, 6, 8, and 10 mg/kg ketamine for stereotyped horizontal locomotion (SHL) assessment using the open field test. Groups B and C were each allotted into three sub-groups (n=7): I, II, and III. They were treated with saline (10 μL/g/body weight) as negative control, 1 mg/kg ketamine and 1.5 mg/kg scopolamine as positive control; and assessed for neurobehavioural effects of acute and repeated administrations using elevated plus-maze (EPM) and Y-maze respectively. Data were presented as Mean ± SEM and analyzed using ANOVA followed by Student-Newman-Keuls test with p < 0.05. The results showed that 1 mg/kg ketamine is devoid of psychotomimetic side effects (1.979, p > 0.05), whereas, ketamine 2, 4, 6, 8 and 10 mg/kg induced significant increase (8.258, p < 0.001), (7.688, p < 0.001), (7.916, p < 0.001), (10.580, p < 0.001) and (13.244, p < 0.001) respectively in SHL compared with the saline group in the open field paradigm. Therefore, ketamine 1 mg/kg was chosen as the sub-psychotomimetic dose. Acute administration of SPDK did not significantly impair memory of mice in both EPM (6.751, p < 0.001) and Y-maze models (3.467, p < 0.05), whereas, its repeated administrations showed comparable results to the group administered scopolamine in both EPM (0.1460, p > 0.8654) and Y-maze models (1.258, p > 0.3126). This study concluded that 1 mg/kg of ketamine may be a sub-psychotomimetic dose; and ketamine-induced psychotomimetic side effects and cognitive impairments could be dose and time-dependent respectively