title: Ventral medial prefrontal cortex inactivation impairs impulse control but does not affect delay-discounting in rats.
abstract: Maladaptive levels of impulsivity are found in several neuropsychiatric disorders, such as ADHD, addiction, aggression and schizophrenia. Intolerance to delay-of-gratification, or delay-discounting, and deficits in impulse control are dissociable forms of impulsivity top-down controlled by the prefrontal cortex, with the ventral medial prefrontal cortex (vmPFC) suggested to be critically involved. The present study used transient inactivation of the rats' vmPFC via bilateral microinfusion of the GABAA receptor agonist muscimol (0.05, 0.5 μg/0.3 μl) to analyse its relevance for impulse control in a 5-choice serial reaction time task (5-CSRTT) and delay-discounting in a Skinner box. Intra-vmPFC injection of low-dose muscimol impaired impulse control indicated by enhanced premature responding in the 5-CSRTT, while flattening the delay-dependent shift in the preference of the large reward in the delay-discounting task. Likewise, high-dose muscimol did not affect delay-discounting, though raising the rate of omissions. On the contrary, 5-CSRTT performance was characterised by deficits in impulse and attentional control. These data support the behavioural distinction of delay-discounting and impulse control on the level of the vmPFC in rats. Reversible inactivation with muscimol revealed an obvious implication of the vmPFC in the modulation of impulse control in the 5-CSRTT. By contrast, delay-discounting processes seem to be regulated by other neuronal pathways, with the vmPFC playing, if at all, a minor role.
authors.affiliation: Department of Neuropharmacology, Brain Research Institute, Center for Cognitive Sciences, University of Bremen, PO Box 330440, 28359 Bremen, Germany. Electronic address: malte.feja@gmx.de.
authors.forename: Malte
authors.initials: M
authors.lastname: Feja
authors.affiliation: Department of Neuropharmacology, Brain Research Institute, Center for Cognitive Sciences, University of Bremen, PO Box 330440, 28359 Bremen, Germany. Electronic address: michael.koch@uni-bremen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists / Q000633:toxicity; D007175:Impulsive Behavior / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D012201:Reward; D013997:Time Factors
chemical_list: D058785:GABA-A Receptor Agonists; D009118:Muscimol
keywords: Delay-discounting; Five-choice serial reaction time task; GABA(A) agonist; Impulsivity; Muscimol