5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder

Behav Brain Res. 2013 Apr 15;243:176-83. doi: 10.1016/j.bbr.2013.01.005. Epub 2013 Jan 14.


Objective: The serotonergic system is implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the distinct role of serotonin (5-HT) receptor subtypes remains unclear. This study investigates the contribution of 5-HT2A and 5-HT2C receptors in the modulation of persistence in the reinforced spatial alternation model of OCD.

Methods: Male Wistar rats were assessed for spontaneous and pharmacologically induced (by m-chlorophenylpiperazine: mCPP) directional persistence in the reinforced alternation OCD model. Systemic administration of mCPP (non-specific 5-HT agonist, 2.5mg/kg), M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084 (selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used. Experiment 1 investigated M100907 and SB242084 effects in animals spontaneously exhibiting high and low persistence during the early stages of alternation training. Experiment 2 investigated M100900 and SB242084 effects on mCPP-induced persistence.

Results: Under the regime used in Experiment 1, 5-HT2A or 5-HT2C receptor antagonism did not affect spontaneous directional persistence in either high or low persistence groups. In Experiment 2, 5-HT2C but not 5-HT2A receptor antagonism significantly reduced, but did not abolish, mCPP-induced directional persistence.

Conclusions: These findings suggest that 5-HT2C but not 5-HT2A receptors contribute to the modulation of mCPP-induced persistent behaviour, raising the possibility that the use of 5-HT2C antagonists may have a therapeutic value in OCD.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Male
  • Obsessive-Compulsive Disorder / chemically induced
  • Obsessive-Compulsive Disorder / metabolism*
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A / physiology*
  • Receptor, Serotonin, 5-HT2C / physiology*
  • Reinforcement, Psychology*
  • Serotonin 5-HT2 Receptor Antagonists / administration & dosage
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology


  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Receptor Agonists