Ketamine attenuates the effects of intermittent social defeat on anxiety, social interaction and cocaine-induced conditioned place preference in male mice
This study investigated whether ketamine could prevent behavioural and addiction-related consequences of intermittent social defeat (ISD) stress during adolescence in male mice. ISD is commonly used as a preclinical model of social stress, depression, and vulnerability to drug addiction
“Mice exposed to intermittent social defeat (ISD) stress in late adolescence exhibit short-term anxiety- and depression-like behaviours and demonstrate greater sensitivity to the rewarding effects of cocaine in adulthood. Furthermore, the development of depression-like symptoms predicts subsequent enhanced vulnerability to cocaine reward.
The aim of this study was to investigate whether ketamine, a non-competitive glutamate N-methyl-D-aspartate (NMDA) receptor antagonist with antidepressant properties, could prevent the short-term effects of ISD on anxiety- and depression-like behaviours and the long-term effects of ISD on the cocaine-induced conditioned place preference. Four groups of late adolescent C57BL/6 male mice were used. One non-stressed group (control) and three ISD-exposed groups treated with ketamine (0, 10 or 30 mg/kg).
After the last defeat episode, the mice were tested in the elevated plus maze, social interaction, splash and tail suspension tests. Three weeks later, the mice were conditioned with cocaine (1 mg/kg).
Stressed mice showed anxiety, displayed a deficit in social interaction, spent less time immobile in the tail suspension test and developed a cocaine place preference. Ketamine attenuated ISD-induced anxiety, social avoidance and cocaine reward potentiation. These results support the usefulness of ketamine in preventing some effects of social stress.”
Martínez-Caballero MA, García-Pardo MP, Calpe-López C, Arenas MC, Manzanedo C, Aguilar MA. Ketamine attenuates the effects of intermittent social defeat on anxiety, social interaction and cocaine-induced conditioned place preference in male mice. Physiol Behav. 2026 Mar 1;305:115189. doi: 10.1016/j.physbeh.2025.115189. Epub 2025 Nov 27. PMID: 41318047. Read Paper
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