Effects of orbital prefrontal cortex dopamine depletion 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. We recently found that destruction of the OPFC disrupted inter-temporal choice in rats. It is not known whether the dopaminergic projection to the OPFC contributes to the regulation of inter-temporal choice. Objective: A quantitative method was used to compare intertemporal choice in rats whose OPFC had been depleted of dopamine with that of sham-lesioned control rats. Methods: Under halothane anaesthesia, rats received injections of 6-hydroxydopamine into the OPFC (2 μg μl ^-1, 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. Concentrations of monoamines in the OPFC were determined by high-performance liquid chromatography at the end of the experiment. Results: In both groups, d_B(50) increased linearly with d_A (r²>0.9 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. When delays of 4 or 8 s were imposed on the smaller reinforcer, the lesioned rats showed greater tolerance of delay to the larger reinforcer (i.e. they exhibited longer values of d_B(50)) than the sham-lesioned rats. Dopamine, noradrenaline and 5-hydroxytryptamine levels in the OPFC of the lesioned group were 20, 75 and 98% of those of the shamlesioned group. Conclusions: The results indicate that dopaminergic afferents to the OPFC contribute to the regulation of inter-temporal choice behaviour due to their role in determining organisms' sensitivity both to reinforcer size and to delay of reinforcement.