title: Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD).
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model.
  
  
  METHODS
  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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1280 Main Street West, Health Science Centre, Room 4N82, Hamilton, Ontario, Canada, L8S 4K1.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Tucci
authors.forename: Anna
authors.initials: A
authors.lastname: Dvorkin-Gheva
authors.forename: Renee
authors.initials: R
authors.lastname: Sharma
authors.forename: Leena
authors.initials: L
authors.lastname: Taji
authors.forename: Paul
authors.initials: P
authors.lastname: Cheon
authors.forename: John
authors.initials: J
authors.lastname: Peel
authors.forename: Ashley
authors.initials: A
authors.lastname: Kirk
authors.forename: Henry
authors.initials: H
authors.lastname: Szechtman
mesh_terms: D000818:Animals; D003192:Compulsive Behavior / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D019257:Quinpirole; D051381:Rats; D020318:Rats, Long-Evans; D050637:Receptors, Dopamine D3 / Q000819:agonists; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D050637:Receptors, Dopamine D3; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; C015068:1-(3-chlorophenyl)piperazine