title: Clomipramine, but not haloperidol or aripiprazole, inhibits quinpirole-induced water contrafreeloading, a putative animal model of compulsive behavior.
abstract: BACKGROUND
  Repeated administrations of the D2/D3 agonist quinpirole (QNP) to rats elicit an antieconomical pattern of drinking called "contrafreeloading" (CFL), a putative model of compulsive-like behavior.
  
  
  OBJECTIVE
  We tested the sensitivity of QNP-induced CFL to haloperidol (HAL), aripiprazole (ARI), and clomipramine (CIM), the latter proven effective in the treatment of obsessive-compulsive disorder (OCD).
  
  
  METHODS
  Rats were trained under a schedule of reinforcement (FR3) for water. On days 1-6, water was only available through lever pressing. On days 7-15, a choice between operant and free access was provided. QNP 0.5 mg/kg was administered alone or in combination with HAL (0.1 or 0.2 mg/kg), ARI (0.3 or 1 mg/kg), or CIM (5 or 10 mg/kg).
  
  
  RESULTS
  Acutely QNP suppressed operant behavior and, therefore, water intake; upon repeated administrations, tolerance developed to this suppressant effect on responding but only to a lesser extent to the antidipsic effect. In choice conditions, QNP induced a progressive preference for the operant access (CFL). HAL per se, but not CIM and ARI, significantly reduced both responding and drinking (operant phase). In the choice phase, HAL and CIM inhibited CFL, but only the latter reinstated total water intake. ARI, in combination with QNP, increased responding.
  
  
  CONCLUSIONS
  CIM reinstates control patterns of drinking, while HAL and ARI where partially or not effective at all, respectively. As far as CIM is considered a first line treatment in OCD, these results further strengthen the notion that QNP-induced CFL belongs to the realm of dopaminergic drug-induced compulsive behaviors.
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: De Carolis
authors.forename: Chiara
authors.initials: C
authors.lastname: Schepisi
authors.forename: Michele S
authors.initials: MS
authors.lastname: Milella
authors.forename: Paolo
authors.initials: P
authors.lastname: Nencini
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000068180:Aripiprazole; D002997:Clomipramine / Q000008:administration & dosage / Q000494:pharmacology*; D003192:Compulsive Behavior / Q000139:chemically induced / Q000517:prevention & control*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D010879:Piperazines; D015363:Quinolones; D019257:Quinpirole; D000068180:Aripiprazole; D006220:Haloperidol; D002997:Clomipramine