title: Effects of ketamine exposure on dopamine concentrations and dopamine type 2 receptor mRNA expression in rat brain tissue.
abstract: OBJECTIVE
  To explore the effects of ketamine abuse on the concentration of dopamine (DA), a monoamine neurotransmitter, and the mRNA expression of dopamine type 2 (D2) receptors in brain tissue, we used male Wistar rats to model ketamine abuse through chronic intraperitoneal infusion of ketamine across different doses.
  
  
  METHODS
  The rats were sacrificed 45 minutes and 1, 2, and 3 weeks after initiating the administration of ketamine or normal saline, as well as 3 days following discontinuation. Brain tissue was harvested to examine the concentration of 2,5-dihydroxyphenylacetic acid and homovanillic acid, the primary metabolites of DA, as well as the expression of D2 receptor mRNA. In addition, behavioral changes were observed within 30 minutes of administration, and withdrawal symptoms were also documented. A factorial experimental design was used to investigate variations and correlations in the primary outcome measures across the four doses and five time points. Brain DA concentrations were significantly higher in the ketamine-treated groups compared with the saline-treated group, with 30 mg/kg > 10 mg/kg > 60 mg/kg > saline (P < 0.05). The D2 receptor mRNA expression exhibited an inverse downregulation pattern, with 30 mg/kg < 10 mg/kg < 60 mg/kg < saline (P < 0.05). In the 10 mg/kg and 30 mg/kg ketamine-treated groups, the DA concentration and D2 receptor mRNA level in the brain tissue correlated with the dose of ketamine (r = 0.752, r = -0.806), but no significant correlation was found in the 60 mg/kg group.
  
  
  RESULTS
  These findings indicated that chronic dosing with ketamine increased the concentration of DA in rat brain tissue by increasing DA release or interrupting DA degradation. D2 receptor mRNA expression likely decreased because of stimulation with excessive DA.
  
  
  CONCLUSIONS
  High-dose (60 mg/kg) ketamine had potent paralyzing effects on the central nervous system of rats and weakened the excitatory effects of the limbic system. Brain DA and D2 receptor mRNA may be associated with ketamine abuse.
authors.affiliation: Department of Forensic Medicine, Shanxi Medical University Taiyuan 030001, Shanxi, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Beijing Wits Medical Consulting Co., Ltd Beijing 100853, P.R. China.
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Shanxi Medical University Taiyuan 030001, Shanxi, P.R. China.
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Wu
authors.affiliation: Department of Forensic Medicine, Shanxi Medical University Taiyuan 030001, Shanxi, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Forensic Medicine, Shanxi Medical University Taiyuan 030001, Shanxi, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Forensic Medicine, Shanxi Medical University Taiyuan 030001, Shanxi, P.R. China.
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Wei
authors.affiliation: Department of Forensic Medicine, Shanxi Medical University Taiyuan 030001, Shanxi, P.R. China.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Wang
keywords: Ketamine; abuse; dopamine; dopamine type 2 receptor mRNA; rat brain