N-acetylcysteine blocks serotonin 1B agonist-induced OCD-related behavior in mice

Behav Neurosci. 2018 Aug;132(4):258-268. doi: 10.1037/bne0000251. Epub 2018 Jul 9.


Glutamate-modulating agents are of increasing interest in obsessive-compulsive disorder (OCD). Current pharmacotherapies for OCD target the serotonin and dopamine systems, and are limited in efficacy. N-acetylcysteine (NAC) is an over-the-counter amino acid supplement that inhibits glutamate neurotransmission and has been shown in preliminary studies to reduce symptoms in OCD and related compulsive disorders. Despite growing interest in NAC as a novel psychiatric medication, no studies currently exist examining the effects of NAC in animal models of compulsive disorders. Here, we investigate NAC in a well-validated mouse model of OCD that is predictive of treatment efficacy as well as the time course for therapeutic onset of OCD medications. NAC (60 mg/kg/day or 120 mg/kg/day) was administered via the drinking water of mice for 3 weeks prior to behavioral testing. Mice were tested in the delayed alternation task (DAT) and open field test following acute serotonin 1B receptor (5-HT1B) agonist challenge to induce OCD-related behavior. We found that both doses of NAC blocked 5-HT1B agonist-induced deficits on the DAT. In a separate study, we administered NAC (60 mg/kg/day) for 1 week or 3 weeks in the drinking water of mice prior to examining OCD-related behavior. We found that blockade of 5-HT1B agonist-induced OCD-like behavior is present at 3 weeks, but not 1 week, of NAC treatment. Together, our findings suggest that NAC is a novel OCD treatment with potential utility as monotherapy and therapeutic effects that emerge on a time-course similar to established medications. (PsycINFO Database Record

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / pharmacology*
  • Animals
  • Disease Models, Animal
  • Free Radical Scavengers / administration & dosage
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Male
  • Mice
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / metabolism
  • Receptor, Serotonin, 5-HT1B / metabolism*
  • Task Performance and Analysis*


  • Free Radical Scavengers
  • Receptor, Serotonin, 5-HT1B
  • Acetylcysteine