title: Effects of quinolinic acid-induced lesions of the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis.
abstract: BACKGROUND
  Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals.
  
  
  OBJECTIVE
  A quantitative method was used to analyse inter-temporal choice in rats with lesions of the OPFC and sham-lesioned control rats.
  
  
  METHODS
  Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 micro l; two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 micro l of the sucrose solution after a delay d (A); a press on B resulted in delivery of 100 micro l of the same solution after a delay d (B). d (B) was increased progressively across successive blocks of six trials in each session, while d (A) was manipulated systematically across phases of the experiment. The indifference delay, d (B(50)) (value of d (B) corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d (B(50)) versus d (A) were derived, and the parameters of the function compared between the groups. The locations of the lesions were verified histologically at the end of the experiment.
  
  
  RESULTS
  In both groups, d (B(50)) increased linearly with d (A) ( r(2)>0.98 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. The brains of the lesioned rats showed extensive atrophy/gliosis of the OPFC, with sparing of the dorsolateral prefrontal cortex.
  
  
  CONCLUSIONS
  The results indicate that lesions of the OPFC can alter inter-temporal choice, either promoting or suppressing "impulsive choice", depending upon the relative sizes and delays of the two choice alternatives. Theoretical analysis based on a quantitative model of inter-temporal choice indicates that the pattern of effect of the OPFC lesion is likely to reflect two actions: (i) an increase in the rate of time discounting; (ii) an increase in sensitivity to the ratio of the sizes of two reinforcers.
authors.affiliation: Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kheramin
authors.forename: S
authors.initials: S
authors.lastname: Body
authors.forename: S
authors.initials: S
authors.lastname: Mobini
authors.forename: M-Y
authors.initials: MY
authors.lastname: Ho
authors.forename: D N
authors.initials: DN
authors.lastname: Velázquez-Martinez
authors.forename: C M
authors.initials: CM
authors.lastname: Bradshaw
authors.forename: E
authors.initials: E
authors.lastname: Szabadi
authors.forename: J F W
authors.initials: JF
authors.lastname: Deakin
authors.forename: I M
authors.initials: IM
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D007175:Impulsive Behavior / Q000139:chemically induced*; D016014:Linear Models; D009498:Neurotoxins / Q000633:toxicity; D009915:Orbit / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology
chemical_list: D009498:Neurotoxins; D017378:Quinolinic Acid