title: The role of medial prefrontal cortical dopamine in spontaneous flexibility in the rat.
abstract: In rat studies, both lesions in the medial prefrontal cortex (mPFC) and alterations of the level of mPFC dopamine (DA) have been found to induce disturbances in behavioural flexibility, as measured with switching tasks. It is not clear whether mPFC DA is also involved in spontaneous flexibility. Therefore, the aim of the present study was to investigate the role of mPFC DA in spontaneous flexibility. As a measure for spontaneous flexibility, the diversity in spatial distribution of exploration on a large open field was used. The rats received local injections into the mPFC with a D1 or D2 antagonist, or the dopamimetic, amphetamine. The results showed that both DA antagonists reduced spontaneous flexibility, due to increased stimulus-bound behaviour. Amphetamine had a similar effect to the DA antagonists. It is suggested that this is most likely due to an amphetamine-induced increase in extracellular DA, leading to a suboptimal level of mPFC DA.
authors.affiliation: Department of Psychoneuropharmacology, University Medical Centre St. Radboud, Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Lanser
authors.forename: B A
authors.initials: BA
authors.lastname: Ellenbroek
authors.forename: F G
authors.initials: FG
authors.lastname: Zitman
authors.forename: D J
authors.initials: DJ
authors.lastname: Heeren
authors.forename: A R
authors.initials: AR
authors.lastname: Cools
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001931:Brain Mapping; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011340:Problem Solving / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C058081:ecopipam; D013469:Sulpiride; D000661:Amphetamine; D004298:Dopamine