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Effects of orbital prefrontal cortex dopamine depletion on inter-temporal choice: a quantitative analysis

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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. 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 inter-temporal 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 (r 2>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 sham-lesioned 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.

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Acknowledgements

This work was supported by a grant from the Wellcome Trust to C.M.B. and E.S. (University of Nottingham) and J.F.W.D. and I.M.A. (University of Manchester). D.N.V.-M. was supported by grants from CONACYT (#25090-H) and Universidad Nacional Autónoma de México DGAPA (#229981). We are grateful to Mrs. Victoria Bak and Mr. R.W. Langley for skilled technical help.

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Author notes

  1. M.-Y. Ho

    Present address: Institute of Clinical Behavioral Sciences, Chang Gung University, Tao Yuan, 333, Taiwan, ROC

  2. D. N. Velázquez-Martinez

    Present address: Departamento Psicofisiologia, Facultad de Psicologia, Universidad Nacional Autónoma de México, Mexico, D.F. 04510, Mexico

Authors and Affiliations

  1. Psychopharmacology Section, Division of Psychiatry, Queen’s Medical Centre, University of Nottingham, Room B109, Medical School, Nottingham, NG7 2UH, UK

    S. Kheramin, S. Body, C. M. Bradshaw & E. Szabadi

  2. Neuroscience & Psychiatry Unit, School of Psychiatry & Behavioural Sciences, University of Manchester, G907, Stopford Building, Oxford Road, Manchester, M13 9PT, UK

    J. F. W. Deakin & I. M. Anderson

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  1. S. Kheramin
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Correspondence to C. M. Bradshaw.

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Kheramin, S., Body, S., Ho, MY. et al. Effects of orbital prefrontal cortex dopamine depletion on inter-temporal choice: a quantitative analysis. Psychopharmacology 175, 206–214 (2004). https://doi.org/10.1007/s00213-004-1813-y

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