title: Aripiprazole blocks acute self-administration of cocaine and is not self-administered in mice.
abstract: BACKGROUND
  The novel antipsychotic aripiprazole in use for treatment of schizophrenia is a partial agonist at dopamine D2 receptors with actions at a variety of other receptors as well. Cocaine is believed to exert an important part of its rewarding effect by increasing extracellular levels of dopamine that subsequently act at dopamine D2 receptors.
  
  
  OBJECTIVE
  As a partial agonist, aripiprazole may antagonize effects at D2 receptors and we accordingly tested whether aripiprazole could antagonize self-administration of cocaine. Because D2-like receptor agonists are self-administered, a D2 receptor partial agonist like aripiprazole might itself be reinforcing. Thus, we also assessed whether mice would acquire self-administration of aripiprazole.
  
  
  METHODS
  A single session, mouse self-administration procedure was used.
  
  
  RESULTS
  Oral pretreatment with aripiprazole dose-dependently decreased cocaine self-administration under a fixed ratio 1 schedule at the peak cocaine dose (0.03 mg/kg/infusion), reaching significance at 0.2 and 0.4 mg/kg of aripiprazole. Using 0.4 mg/kg, aripiprazole decreased rates of cocaine self-administration without shifting the peak of the dose-response function. There was no effect of aripiprazole per se, suggesting that its inhibitory action was due to effects on cocaine self-administration rather than non-specific motor effects. Aripiprazole was not found to be self-administered in the tested dose range (0.0003-0.3 mg/kg/infusion). The three highest doses (0.03, 0.1, and 0.3 mg/kg/infusion) even caused significant decreases in nose-poking activity, possibly due to extrapyramidal side effects.
  
  
  CONCLUSIONS
  These data are consistent with a potential role for aripiprazole in treatment of cocaine addiction without abuse potential per se.
authors.affiliation: Laboratory of Neuropsychiatry, Rigshospitalet University Hospital, University of Copenhagen, 9 Blegdamsvej, DK-2100, Copenhagen, Denmark.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sørensen
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Sager
authors.forename: Jørgen H
authors.initials: JH
authors.lastname: Petersen
authors.forename: Lise T
authors.initials: LT
authors.lastname: Brennum
authors.forename: Peter
authors.initials: P
authors.lastname: Thøgersen
authors.forename: Cecilie
authors.initials: C
authors.lastname: Hee Bengtsen
authors.forename: Morgane
authors.initials: M
authors.lastname: Thomsen
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.forename: David P D
authors.initials: DP
authors.lastname: Woldbye
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001921:Brain / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D012646:Self Administration
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D000068180:Aripiprazole; D003042:Cocaine