title: Effect of GBR12909 on affective behavior: distinguishing motivational behavior from antidepressant-like and addiction-like behavior using the runway model of intracranial self-stimulation.
abstract: BACKGROUND
  It was recently demonstrated that the priming stimulation effect (PSE) in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this novel experimental model have not been fully clarified.
  
  
  OBJECTIVE
  To elucidate the involvement of dopamine uptake inhibition in motivated behavior and the difference in experimental characteristics between closely related experimental models, we investigated the effects of the dopamine uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test (FST), and on conditioned place preference (CPP). In addition, the role of dopamine receptor signaling in the runway model was evaluated using dopamine receptor agonists and antagonists.
  
  
  RESULTS
  GBR12909 dose-dependently increased running speed on the runway and decreased immobility time in the FST without affecting the time spent in the drug-associated compartment in CPP tests. The effect of GBR12909 in the runway model was inhibited by pre-treatment with the dopamine receptor antagonists haloperidol and raclopride. The dopamine receptor agonists SKF38393 and quinpirole dose-dependently decreased running speed.
  
  
  CONCLUSIONS
  These results demonstrate that GBR12909 displays motivation-enhancing and antidepressant-like effects without place conditioning effects. In addition, the mechanisms of PSE enhancement in the runway ICSS model are different from those underlying closely associated experimental models and are mediated by increases in dopamine signaling.
authors.affiliation: Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Esumi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sagara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nakamoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Gomita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004567:Electrodes, Implanted; D007031:Hypothalamus / Q000187:drug effects* / Q000601:surgery; D008297:Male; D009042:Motivation / Q000187:drug effects*; D009483:Neuropsychological Tests; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012653:Self Stimulation / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000503:physiopathology
chemical_list: C461261:(1-(2-(bis(4-fluorophenyl)methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate); D018765:Dopamine Uptake Inhibitors; D010879:Piperazines