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

Abstract

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 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.