title: N-acetylcysteine decreased nicotine reward-like properties and withdrawal in mice.
abstract: BACKGROUND
  N-acetylcysteine can increase extrasynaptic glutamate and reduce nicotine self-administration in rats and smoking rates in humans.
  
  
  OBJECTIVE
  The aim of this study was to determine if N-acetylcysteine modulates the development of nicotine place conditioning and withdrawal in mice.
  
  
  METHODS
  N-acetylcysteine was given to nicotine-treated male ICR mice. Experiment 1: reward-like behavior. N-acetylcysteine (0, 5, 15, 30, or 60 mg/kg, i.p.) was given 15 min before nicotine (0.5 mg/kg, s.c.) or saline (10 ml/kg, s.c.) in an unbiased conditioned place preference (CPP) paradigm. Conditioning for highly palatable food served as control. Experiment 2: spontaneous withdrawal. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on anxiety-like behavior, somatic signs, and hyperalgesia was measured 18-24 h after continuous nicotine (24 mg/kg/day, 14 days). Experiment 3: mecamylamine-precipitated, withdrawal-induced aversion. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on mecamylamine (3.5 mg/kg, i.p.)-precipitated withdrawal was determined after continuous nicotine (24 mg/kg, i.p., 28 days) using the conditioned place aversion (CPA) paradigm.
  
  
  RESULTS
  Dose-related reductions in the development of nicotine CPP, somatic withdrawal signs, hyperalgesia, and CPA were observed after N-acetylcysteine pretreatment. No effect of N-acetylcysteine was found on palatable food CPP, anxiety-like behavior, or motoric capacity (crosses between plus maze arms). Finally, N-acetylcysteine did not affect any measure in saline-treated mice at doses effective in nicotine-treated mice.
  
  
  CONCLUSIONS
  These are the first data suggesting that N-acetylcysteine blocks specific mouse behaviors associated with nicotine reward and withdrawal, which adds to the growing appreciation that N-acetylcysteine may have high clinical utility in combating nicotine dependence.
authors.affiliation: Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA. msbowers@vcu.edu.|Virginia Institute for Psychiatric and Behavioral Genetics Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, 23298, USA. msbowers@vcu.edu.
authors.forename: M S
authors.initials: MS
authors.lastname: Bowers
authors.affiliation: Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Maldoon
authors.affiliation: Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000009:adverse effects*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D014029:Tobacco Use Disorder / Q000188:drug therapy
chemical_list: D008464:Mecamylamine; D009538:Nicotine; D000111:Acetylcysteine
keywords: Conditioned place aversion; Conditioned place preference; Mice; N-acetylcysteine; Nicotine; Reward; Withdrawal