Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit

Behav Pharmacol. 2013 Feb;24(1):65-73. doi: 10.1097/FBP.0b013e32835d5b7a.


This study investigated whether the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) can induce compulsive checking in a large open field, as does the dopamine D2/D3 receptor agonist quinpirole. To induce compulsive checking, male rats were exposed to eight injections of either 8-OH-DPAT (1 mg/kg), quinpirole (0.2 mg/kg), or saline. Subsequently, to assess cross-sensitization, rats received an acute challenge of 8-OH-DPAT or quinpirole. The results showed that treatment with 8-OH-DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole. However, there was no cross-sensitization between 8-OH-DPAT and quinpirole on measures of compulsive checking and locomotion. Moreover, the spatial distribution of locomotor paths in 8-OH-DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals. Thus, although 8-OH-DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently. It is suggested that 8-OH-DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive-compulsive disorder. Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check. Conversely, 8-OH-DPAT may perpetuate the activated motivational state by inhibiting the serotonergic-negative feedback signals that normally deactivate the obsessive-compulsive disorder circuit.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / toxicity*
  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Compulsive Behavior / chemically induced
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Drug Interactions
  • Male
  • Nerve Tissue Proteins / agonists*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Obsessive-Compulsive Disorder / chemically induced*
  • Quinpirole / toxicity*
  • Random Allocation
  • Rats
  • Rats, Long-Evans
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / metabolism
  • Serotonin 5-HT1 Receptor Agonists / toxicity
  • Serotonin 5-HT2 Receptor Agonists / toxicity
  • Serotonin 5-HT3 Receptor Agonists / toxicity
  • Serotonin Receptor Agonists / toxicity*
  • Spatial Behavior / drug effects


  • Nerve Tissue Proteins
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT3 Receptor Agonists
  • Serotonin Receptor Agonists
  • Quinpirole
  • 8-Hydroxy-2-(di-n-propylamino)tetralin