Docosahexaenoic acid intake ameliorates ketamine-induced impairment of spatial cognition and learning ability in ICR mice

• Chronic ketamine exposure leads to persistent spatial cognitive impairment.
• DHA would be a promising therapy to improve this cognitive impairment.
• Beneficial effect of DHA is correlated with the up-regulation of GABA levels.

Several studies have reported the ketamine-induced cognitive impairment. Docosahexaenoic acid (DHA) supplementation improves cognitive function in human infants and protects against learning impairment in patients with Alzheimer's disease (AD). In this study, we investigated the effect of DHA on ketamine-induced impairment of spatial cognition and learning ability in Institute of Cancer Research (ICR) mice. Morris water maze (MWM) was used to assess spatial learning and memory. Gamma-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex were measured using high-performance liquid chromatography (HPLC). The results showed that intraperitoneal injection of ketamine (30 mg/kg, twice per day) for 4 weeks led to the decline of spatial cognitive ability in mice, and 420 mg/(kg d) DHA supplementation for 6 weeks improved ketamine-induced spatial cognitive impairment to a certain extent. The up-regulation of GABA levels in the hippocampus and prefrontal cortex was related to the improvement in spatial learning. Our results suggested that DHA supplementation would be a promising intervention to improve ketamine-induced spatial memory and cognitive dysfunction, and this effect of DHA might be correlated with the up-regulation of GABA levels.