title: Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A₂AKO mice.
abstract: BACKGROUND
  Mesolimbic dopamine (DA) regulates behavioral activation and effort-related decision-making in motivated behaviors. Mesolimbic DA D2 receptors are co-localized with adenosine A2A receptors, and they interact in an antagonistic manner.
  
  
  OBJECTIVE
  A T-maze task was developed to assess dopaminergic involvement in preference between a reinforcer that involves vigorous voluntary activity (running wheel) and a reinforcer that requires minimal behavioral activation (sucrose pellets). Haloperidol (D2 antagonist) was administered to adenosine A2A receptor knockout (A2AKO) and wild-type (WT) littermate controls to assess the involvement of these two receptors in the selection of running wheel activity versus sucrose consumption.
  
  
  RESULTS
  Under control conditions, mice spent more time running and less time eating. In WT mice, haloperidol reduced time running but actually increased time-consuming sucrose. However, A2AKO mice did not show the haloperidol-induced shift from running wheel activity to sucrose intake. Prefeeding reduced sucrose consumption in the T-maze in both strains, indicating that this paradigm is sensitive to motivational devaluation. Haloperidol increased c-Fos immunoreactivity in anterior cingulate cortex (ACg) and nucleus accumbens (Acb) core of WT but not KO mice.
  
  
  CONCLUSIONS
  These results indicate that after DA antagonism, the preference for vigorous physical activity is reduced, while palatable food selection increases. Adenosine A2A receptor deletion provides resistance to these effects of D2 receptor antagonism. These two receptors in Acb core and ACg seem to be involved in the regulation of the intrinsic reinforcing characteristics of voluntary exercise but not in the regulation of the primary reinforcing characteristics of palatable sedentary reinforcers.
authors.affiliation: Department of Psychobiology, Universitat Jaume I, Castelló, Spain. correa@uji.es.
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
authors.affiliation: Department of Psychobiology, Universitat Jaume I, Castelló, Spain. mpardodoc@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Department of Psychobiology, Universitat Jaume I, Castelló, Spain. pili.bayarri@hotmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Bayarri
authors.affiliation: Department of Psychobiology, Universitat Jaume I, Castelló, Spain. lcruz@psb.uji.es.
authors.forename: Laura
authors.initials: L
authors.lastname: López-Cruz
authors.affiliation: Department of Psychobiology, Universitat Jaume I, Castelló, Spain. nsanmigu@uji.es.
authors.forename: Noemí
authors.initials: N
authors.lastname: San Miguel
authors.affiliation: Department of Experimental and Health Sciences, Universitat Pompeu Fabra and IMIM-Hospital del Mar Research Institute, Barcelona, Spain. olga.valverde@upf.edu.
authors.forename: Olga
authors.initials: O
authors.lastname: Valverde
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, IRIBHM, Bruxelles, Belgium. cledent@ulb.ac.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT, USA. john.salamone@uconn.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000523:psychology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics*
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D013395:Sucrose; D006220:Haloperidol; D004298:Dopamine
keywords: Accumbens; Cingulate; Reward; Running wheel; Sucrose