Effects of quinolinic acid-induced lesions of the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis

Rationale: 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 μl; 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 μl of the sucrose solution after a delay d A ; a press on B resulted in delivery of 100 μl 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 dA (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.