, Volume 231, Issue 18, pp 3707–3718 | Cite as

Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD)

  • Mark C. Tucci
  • Anna Dvorkin-Gheva
  • Renee Sharma
  • Leena Taji
  • Paul Cheon
  • John Peel
  • Ashley Kirk
  • Henry SzechtmanEmail author
Original Investigation



Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking.


The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model.


Four groups of male rats (N = 14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP.


Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only.


Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.


Compulsive checking behavior Dopamine-serotonin interaction Security motivation mCPP Quinpirole 



We thank Ms. Dawn Graham for excellent technical assistance in carrying out this study and Dr Erik Woody for advise with statistical analysis. This study was supported by operating grants to HS from the Canadian Institutes of Health Research (CIHR MOP-64424), the Natural Sciences and Engineering Research Council of Canada (RGPIN A0544), and the Ontario Mental Health Foundation, and by an Ontario Graduate Scholarship award to MCT.

Conflict of interest

The authors declare no conflict of interests.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mark C. Tucci
    • 1
  • Anna Dvorkin-Gheva
    • 1
  • Renee Sharma
    • 1
  • Leena Taji
    • 1
  • Paul Cheon
    • 1
  • John Peel
    • 1
  • Ashley Kirk
    • 1
  • Henry Szechtman
    • 1
    Email author
  1. 1.Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada

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