Action of Ketamine on acquisition in the novel object recognition test and the metabolic activity in hippocampus

Abstract

Psychotogenic effects of ketamine, due to antagonism of NMDA (N-methyl-D-aspartic acid) glutamate receptors, are widely known, and they are subject of study in our laboratory. In the present study we searched for the effect of systemic administration of ketamine at low doses in the novel object recognition test. Holtzman derived colony rats weighing 240-290 g were used. Novel object recognition test involves variables related to memory and perception. We used an intraperitoneal administration of ketamine in sub-anesthetic doses (1.25, 2.5 and 5 mg / kg ip) 3 min before training. Test was realized 120 min after training. Additionally, groups of five rats treated with saline or different sub-anesthetic doses were paired for measurement of hippocampus metabolic activity 8 min after injection. It was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) through spectrophotometric wavelength measurement. We observed that treatment produced a significant increase in total scan time in the evaluation session (p <0.05) at all doses. It also led to a significant decrease in the discrimination rate (p <0.001) at doses of 2.5 and 5 mg/kg. These findings allow us to postulate that treatment induced an inhibitory effect on short-term memory. Metabolic activity showed an evident and significant decrease in hippocampus (1.25 mg/kg; 2.5 mg/kg, p<0.001). We conclude that systemically administered ketamine in low doses produces inhibitory effect on short-term memory. These behavioral findings are accompanied by a decrease in metabolic activity in the hippocampus.