title: Docosahexaenoic acid intake ameliorates ketamine-induced impairment of spatial cognition and learning ability in ICR mice.
abstract: 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 (30mg/kg, twice per day) for 4 weeks led to the decline of spatial cognitive ability in mice, and 420mg/(kgd) 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.
authors.affiliation: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, China.
authors.forename: Shucai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Brain Hospital of Hunan Province, Changsha, Hunan, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.affiliation: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, China. Electronic address: hxchenchina@gmail.com.
authors.forename: Hongxian
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D013287:Illicit Drugs / Q000633:toxicity*; D007649:Ketamine / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008813:Mice, Inbred ICR; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D013287:Illicit Drugs; D004281:Docosahexaenoic Acids; D005680:gamma-Aminobutyric Acid; D007649:Ketamine
keywords: Docosahexaenoic acid; Gamma-aminobutyric acid; Ketamine; Spatial learning ability