Psychopharmacology

, Volume 195, Issue 1, pp 71–84 | Cite as

Effects of quinolinic acid-induced lesions of the nucleus accumbens core on inter-temporal choice: a quantitative analysis

  • G. Bezzina
  • T. H. C. Cheung
  • K. Asgari
  • C. L. Hampson
  • S. Body
  • C. M. Bradshaw
  • E. Szabadi
  • J. F. W. Deakin
  • I. M. Anderson
Original Investigation

Abstract

Rationale

There is evidence that lesions of the nucleus accumbens core (AcbC) promote preference for smaller earlier reinforcers over larger delayed reinforcers in inter-temporal choice paradigms. It is not known whether this reflects an effect of the lesion on the rate of delay discounting, on sensitivity to reinforcer magnitude, or both.

Aim

We examined the effect of AcbC lesions on inter-temporal choice using a quantitative method that allows effects on delay discounting to be distinguished from effects on sensitivity to reinforcer size.

Materials and methods

Sixteen rats received bilateral quinolinic acid-induced lesions of the AcbC; 14 received sham lesions. They were trained under a discrete-trials progressive delay schedule to press two levers (A and B) for a sucrose solution. Responses on A delivered 50 μl of the solution after a delay d A; responses on B delivered 100 μl after d B. d B increased across blocks of trials, while d A was manipulated across phases of the experiment. Indifference delay d B(50) (value of d B corresponding to 50% choice of B) was estimated in each phase, and linear indifference functions (d B(50) vs d A) derived.

Results

dB(50) increased linearly with dA (r2 > 0.95 in each group). The intercept of the indifference function was lower in the lesioned than the sham-lesioned group; slope did not differ between groups. The lesioned rats had extensive neuronal loss in the AcbC.

Conclusions

The results confirm that lesions of the AcbC promote preference for smaller, earlier reinforcers and suggest that this reflects an effect of the lesion on the rate of delay discounting.

Keywords

Quinolinic acid Excitotoxin Lesion Nucleus accumbens Inter-temporal choice Delay of reinforcement Delay discounting Rat 

Notes

Acknowledgements

This work was supported by the Wellcome Trust. We are grateful to Ms. V.K. Bak and Mr R.W. Langley for skilled technical help.

References

  1. Acheson A, Farrar AM, Patak M, Hausknecht KA, Kieres AK, Choi S, de Wit H, Richards JB (2006) Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to reinforcement. Behav Brain Res 173:217–228PubMedCrossRefGoogle Scholar
  2. Ainslie G (1975) Specious reward: a behavioral theory of impulsiveness and impulse control. Psychol Bull 82:463–496PubMedCrossRefGoogle Scholar
  3. Bizot J, Le Bihan C, Puech AJ, Hamon M, Thiebot M (1999) Serotonin and tolerance to delay of reward in rats. Psychopharmacology 146:400–412PubMedCrossRefGoogle Scholar
  4. Bowman EM, Brown VJ (1998) Effects of excitotoxic lesions of the rat ventral striatum on the perception of reward cost. Exp Brain Res 123:439–448PubMedCrossRefGoogle Scholar
  5. Bradshaw CM, Body S, Szabadi E (2007) Decision-making and neuroeconomics: delayed reinforcement, neuroscience. In: Squire L (ed) New encyclopedia of neuroscience, MS#1527. Elsevier, Oxford, (in press)Google Scholar
  6. Cardinal RN (2006) Neural systems implicated in delayed and probabilistic reinforcement. Neural Netw 19:1277–1301PubMedCrossRefGoogle Scholar
  7. Cardinal RN, Robbins TW, Everitt BJ (2000) The effects of d-amphetamine, chlordiazepoxide, alpha-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats. Psychopharmacology 152:362–375PubMedCrossRefGoogle Scholar
  8. Cardinal RN, Pennicott DR, Sugathapala CL, Robbins TW, Everitt BJ (2001) Impulsive choice induced in rats by lesions of the nucleus accumbens core. Science 292:2499–2501PubMedCrossRefGoogle Scholar
  9. Cardinal RN, Robbins TW, Everitt BJ (2003) Choosing delayed rewards: perspectives from learning theory, neurochemistry, and neuroanatomy. In: Heather N, Vuchinich RE (eds) Choice, behavioral economics and addiction. Elsevier, Oxford, pp 183–213Google Scholar
  10. Cardinal RN, Winstanley CA, Robbins TW, Everitt BJ (2004) Limbic corticostriatal systems and delayed reinforcement. Ann N Y Acad Sci 1021:33–50PubMedCrossRefGoogle Scholar
  11. Cheung THC, Cardinal RN (2005) Hippocampal lesions facilitate instrumental learning with delayed reinforcement but induce impulsice choice in rats. BMC Neurosci 6:36PubMedCrossRefGoogle Scholar
  12. Evenden JL, Ryan CN (1996) The pharmacology of impulsive behaviour in rats: The effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology 128:161–170PubMedCrossRefGoogle Scholar
  13. Evenden JL, Ryan CN (1999) The pharmacology of impulsive behaviour in rats VI: the effects of ethanol and selective serotonergic drugs on response choice with varying delays of reinforcement. Psychopharmacology 146:413–421PubMedCrossRefGoogle Scholar
  14. Gibbon J (1977) Scalar expectancy theory and Weber’s law in animal timing. Psychol Rev 84:279–325CrossRefGoogle Scholar
  15. Gibbon J (1991) Origins of scalar timing. Learn Motiv 22:3–38CrossRefGoogle Scholar
  16. Green L, Fisher EB, Perlow S, Sherman L (1981) Preference reversal and self-control—choice as a function of reward amount and delay. Behav Anal Lett 1:43–51Google Scholar
  17. Herrnstein R (1981) Self-control as response strength. In: Bradshaw CM, Szabadi E, Lowe CF (eds) Quantification of steady-state operant behaviour. Elsevier, Amsterdam, pp 3–20Google Scholar
  18. Ho MY, Mobini S, Chiang TJ, Bradshaw CM, Szabadi E (1999) Theory and method in the quantitative analysis of “impulsive choice” behaviour: implications for psychopharmacology. Psychopharmacology 146:362–372PubMedCrossRefGoogle Scholar
  19. Ho M-Y, Velazquez-Martinez DN, Bradshaw CM, Szabadi E (2002) 5-Hydroxytryptamine and interval timing behaviour. Pharmacol Biochem Behav 71:773–785PubMedCrossRefGoogle Scholar
  20. Jongen-Relo AL, Feldon J (2002) Specific neuronal protein: A new tool for histological evaluation of excitotoxic lesions. Physiol Behav 76:449–456PubMedCrossRefGoogle Scholar
  21. Kheramin S, Body S, Mobini S, Ho MY, Velazquez-Martinez DN, Bradshaw CM, Szabadi E, Deakin JFW, Anderson IM (2002) Effects of quinolinic acid-induced lesions of the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis. Psychopharmacology 165:9–17PubMedCrossRefGoogle Scholar
  22. Kheramin S, Body S, Ho MY, Velazquez-Martinez DN, Bradshaw CM, Szabadi E, Deakin JFW, Anderson IM (2003) Role of the orbital prefrontal cortex in choice between delayed and uncertain reinforcers: a quantitative analysis. Behav Processes 64:239–250PubMedCrossRefGoogle Scholar
  23. Kheramin S, Body S, Ho MY, Velazquez-Martinez DN, Bradshaw CM, Szabadi E, Deakin JFW, Anderson IM (2004) Effects of orbital prefrontal cortex dopamine depletion on inter-temporal choice: a quantitative analysis. Psychopharmacology 175:206–214PubMedCrossRefGoogle Scholar
  24. Kheramin S, Body S, Miranda Herrera F, Bradshaw CM, Szabadi E, Deakin JFW, Anderson IM (2005) The effect of orbital prefrontal cortex lesions on performance on a progressive ratio schedule: implications for models of inter-temporal choice. Behav Brain Res 156:145–152PubMedCrossRefGoogle Scholar
  25. Killeen PR (2005) Gradus ad Parnassum: Ascending strength gradients or descending memory traces? Behav Brain Sci 28:432–434CrossRefGoogle Scholar
  26. Killeen PR, Fetterman JG (1988) A behavioral theory of timing. Psychol Rev 95:274–295PubMedCrossRefGoogle Scholar
  27. Killeen PR, Fetterman JG, Bizo LA (1997) Time’s causes. In: Bradshaw CM, Szabadi E (eds) Time and behaviour: psychological and neurobehavioural analyses. Elsevier, AmsterdamGoogle Scholar
  28. Lindstrom MJ, Bates DM (1990) Nonlinear mixed-effects models for repeated measures data. Biometrics 46:673–687PubMedCrossRefGoogle Scholar
  29. Logue AW (1988) Research on self-control: an integrating framework. Behav Brain Sci 11:665–678CrossRefGoogle Scholar
  30. Mazur JE (1987) An adjusting procedure for studying delayed reinforcement. In: Commons ML, Mazur JE, Nevin JA, Rachlin H (eds) Quantitative analyses of behavior: V. The effect of delay and of intervening events on reinforcement value. Lawrence Erlbaum, Hillsdale, New Jersey, pp 55–73Google Scholar
  31. Mazur JE (2006) Mathematical models and the experimental analysis of behavior. J Exp Anal Behav 85:285–291CrossRefGoogle Scholar
  32. Mobini S, Chiang TJ, Al-Ruwaitea AS, Ho MY, Bradshaw CM, Szabadi E (2000a) Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis. Psychopharmacology 149:313–318PubMedCrossRefGoogle Scholar
  33. Mobini S, Body S, Ho M-Y, Bradshaw CM, Szabadi E (2000b) Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement. Psychopharmacology 160:290–298Google Scholar
  34. Monterosso J, Ainslie G (1999) Beyond discounting: possible experimental models of impulse control. Psychopharmacology 146:339–347PubMedCrossRefGoogle Scholar
  35. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, San DiegoGoogle Scholar
  36. Pinheiro JC, Bates DM (2004) Mixed-effects models in S and S-plus. Springer, New YorkGoogle Scholar
  37. Pothuizen HHJ, Jongen-Relo AL, Feldon J, Yee BK (2005) Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive-choice behaviour and salience learning in rats. Eur J Neurosci 22:2605–2616PubMedCrossRefGoogle Scholar
  38. Rachlin H (1974) Self-control. Behaviorism 2:94–107Google Scholar
  39. Rachlin H (2006) Notes on discounting. J Exp Anal Behav 85:425–435PubMedCrossRefGoogle Scholar
  40. Richards JB, Sabol KE, de Wit H (1999) Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology 146:432–439PubMedCrossRefGoogle Scholar
  41. Rudebeck PH, Walton ME, Smyth AN, Bannerman DM, Rushworth FS (2006) Separate neural pathways process different decision costs. Nat Neurosci 9:1161–1168PubMedCrossRefGoogle Scholar
  42. Schwarcz R, Whetsell WO, Mangano RM (1983) Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat-brain. Science 219:316–318PubMedCrossRefGoogle Scholar
  43. Snedecor GW, Cochran WG (1989) Statistical methods, 8th edn. Iowa State University PressGoogle Scholar
  44. Wade TR, de Wit H, Richards JB (2000) Effects of dopaminergic drugs on delayed reward as a measure of impulsive behavior in rats. Psychopharmacology 150:90–101PubMedCrossRefGoogle Scholar
  45. Winstanley CA, Theobald DEH, Dalley JW, Robbins TW (2003) Global 5-HT depletion attenuates the ability of amphetamine to decrease impulsive choice in rats. Psychopharmacology 170:320–331PubMedCrossRefGoogle Scholar
  46. Winstanley CA, Theobald DEH, Cardinal RN, Robbins TW (2004) Contrasting roles for basolateral amygdala and orbitofrontal cortex in impulsive choice. J Neurosci 24:4718–4722PubMedCrossRefGoogle Scholar
  47. Winstanley CA, Baunez C, Theobald DEH, Robbins TW (2005) Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control. Eur J Neurosci 21:3107–3116PubMedCrossRefGoogle Scholar
  48. Wogar MA, Bradshaw CM, Szabadi E (1993) Effects of lesions of the ascending 5-hydroxytryptaminergic pathways on choice between delayed reinforcers. Psychopharmacology 111:239–243PubMedCrossRefGoogle Scholar
  49. Zar JH (1999) Biostatistical analysis, fourth edition. Prentice-Hall, Upper Saddle River, NJGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • G. Bezzina
    • 1
  • T. H. C. Cheung
    • 1
  • K. Asgari
    • 1
  • C. L. Hampson
    • 1
  • S. Body
    • 1
  • C. M. Bradshaw
    • 1
  • E. Szabadi
    • 1
  • J. F. W. Deakin
    • 2
  • I. M. Anderson
    • 2
  1. 1.Psychopharmacology Section, Division of PsychiatryUniversity of NottinghamNottinghamUK
  2. 2.Neuroscience & Psychiatry Unit, Division of Psychiatry & Behavioural SciencesUniversity of ManchesterManchesterUK

Personalised recommendations