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Alterations in effort-related decision-making induced by stimulation of dopamine D1, D2, D3, and corticotropin-releasing factor receptors in nucleus accumbens subregions

  • Courtney A. Bryce
  • Stan B. FlorescoEmail author
Original Investigation
  • 117 Downloads

Abstract

Rationale

Nucleus accumbens (NAc) dopamine (DA) plays an integral role in overcoming effort costs, as blockade of D1 and D2 receptors reduces the choice of larger, more-costly rewards. Similarly, the stress neuropeptide corticotropin-releasing factor (CRF) modulates DA transmission and mediates stress-induced alterations in effort-related choice.

Objectives

The current study explored how excessive stimulation of different DA receptors within the NAc core and shell alters effort-related decision-making and compared these effects to those induced by CRF stimulation.

Methods

Male Long Evans rats were well-trained on an effort-discounting task wherein they choose between a low-effort/low-reward and a high-effort/high-reward lever where the effort requirement increased over blocks (2–20 presses). Dopamine D1 (SKF 81297, 0.2–2 μg), D2/3 (quinpirole, 1–10 μg), or D3 (PD 128,907, 1.5–3 μg) receptor agonists, or CRF (0.5 μg), were infused into the NAc core or shell prior to testing.

Results

Stimulation of D2/3 receptors with quinpirole in the NAc core or shell markedly reduced the choice of high-effort option and increase choice latencies, without altering preference for larger vs smaller rewards. Stimulation of D1 or D3 receptors did not alter choice, although SKF 81297 infusions into the shell reduced response vigor. In comparison, core infusions of CRF flattened the discounting curve, reducing effortful choice when costs were low and increasing it when costs were high.

Conclusions

Excessive stimulation of NAc D2 receptors has detrimental effects on effort-related decision-making. Furthermore, CRF stimulation induces dissociable effects on decision-making compared with those induced the effects of stimulation of different DA receptors.

Keywords

Decision-making Effort Motivation Nucleus accumbens Dopamine D1 receptors D2 receptors D3 receptors Corticotropin-releasing factor Stress Depression Rats 

Notes

Acknowledgements

The authors thank Jade Adalbert for her outstanding assistance with behavioral testing.

Funding information

This work was supported by a grant from the Canadian Institutes of Health Research (MOP 133579) to SBF.

Compliance with ethical standards

All testing was done in accordance with the Canadian Council of Animal Care and the Animal Care Committee of the University of British Columbia.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Baik JH (2013) Dopamine signaling in reward-related behaviors. Front Neural Circuits 7:152.  https://doi.org/10.3389/fncir.2013.00152 CrossRefGoogle Scholar
  2. Bardgett ME, Depenbrock M, Downs N, Points M, Green L (2009) Dopamine modulates effort-based decision making in rats. BehavNeurosci 123:242–251.  https://doi.org/10.1037/a0014625 Google Scholar
  3. Blaes SL, Orsini CA, Mitchell MR, Spurrell MS, Betzhold SM, Vera K, Bizon JL, Setlow B (2018) Monoaminergic modulation of decision-making under risk of punishment in a rat model. Behav Pharmacol 29:745–761CrossRefGoogle Scholar
  4. Bristow LJ, Cook GP, Gay JC, Kulagowski JJ, Landon L, Murray F, Saywell KL, Young L, Hutson PH (1996) The behavioural and neurochemical profile of the putative dopamine D3 receptor agonist, (+)-PD 128907, in the rat. Neuropharmacology 35:285–294.  https://doi.org/10.1016/0028-3908(96)00179-7 CrossRefGoogle Scholar
  5. Bryce CA, Floresco SB (2016) Perturbations in effort-related decision-making driven by acute stress and corticotropin-releasing factor. Neuropsychopharmacology 41:2147–2159.  https://doi.org/10.1038/npp.2016.15 CrossRefGoogle Scholar
  6. Chen YW, Rada PV, Bützler BP, Leibowitz SF, Hoebel BG (2012) Corticotropin-releasing factor in the nucleus accumbens shell induces swim depression, anxiety, and anhedonia along with changes in local dopamine/acetylcholine balance. Neuroscience 206:155–166.  https://doi.org/10.1016/j.neuroscience.2011.12.009 CrossRefGoogle Scholar
  7. Cousins MS, Wei W, Salamone JD (1994) Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs. Psychopharmacology 116:529–537.  https://doi.org/10.1007/BF02247489 CrossRefGoogle Scholar
  8. Depoortere R, Perrault G, Sanger DJ (1996) Behavioural effects in the rat of the putative dopamine D3 receptor agonist 7-OH-DPAT : comparison with quinpirole and apomorphine. Psychopharmacology 124(3):231–240CrossRefGoogle Scholar
  9. Dunn AJ, Berridge CW (1987) Corticotropin-releasing factor administration elicits a stress-like activation of cerebral catecholaminergic systems. Pharmacol Biochem Behav 27:685–691.  https://doi.org/10.1016/0091-3057(87)90195-X CrossRefGoogle Scholar
  10. Filla I, Bailey MR, Schipani E, Winiger V, Mezias C, Balsam PD, Simpson EH (2018) Striatal dopamine D2 receptors regulate effort but not value-based decision making and alter the dopaminergic encoding of cost. Neuropsychopharmacology 43:2180–2189.  https://doi.org/10.1038/s41386-018-0159-9 CrossRefGoogle Scholar
  11. Floresco SB, Tse M, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979.  https://doi.org/10.1038/sj.npp.1301565 CrossRefGoogle Scholar
  12. Ghods-Sharifi S, Floresco SB (2010) Differential effects on effort discounting induced by inactivations of the nucleus accumbens core or shell. Behav Neurosci 124:179–191.  https://doi.org/10.1037/a0018932 CrossRefGoogle Scholar
  13. Haluk DM, Floresco SB (2009) Ventral striatal dopamine modulation of different forms of behavioral flexibility. Neuropsychopharmacology 34:2041–2052.  https://doi.org/10.1038/npp.2009.21 CrossRefGoogle Scholar
  14. Holly EN, Debold JF, Miczek KA (2015) Increased mesocorticolimbic dopamine during acute and repeated social defeat stress: modulation by corticotropin releasing factor receptors in the ventral tegmental area. Psychopharmacology 232:4469–4479.  https://doi.org/10.1007/s00213-015-4082-z CrossRefGoogle Scholar
  15. Kalivas PW, Duffy P (1995) Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress. Brain Res 675:325–328CrossRefGoogle Scholar
  16. Kalivas PW, Duffy P, Latimer LG (1987) Neurochemical and behavioral effects of corticotropin-releasing factor in the ventral tegmental area of the rat. J Pharmacol Exp Ther 242(3):757–763Google Scholar
  17. Korotkova TM, Brown RE, Sergeeva OA, Ponomarenko AA, Haas HL (2006) Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat. Eur J Neurosci 23:2677–2685.  https://doi.org/10.1111/j.1460-9568.2006.04792.x CrossRefGoogle Scholar
  18. Lemos JC, Wanat MJ, Smith JS, Reyes BAS, Hollon NG, van Bockstaele EJ, Chavkin C, Phillips PEM (2012) Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive. Nature 490:402–406.  https://doi.org/10.1038/nature11436 CrossRefGoogle Scholar
  19. Mata F, Treadway M, Kwok A, Truby H, Yücel M, Stout JC, Verdejo-Garcia A (2017) Reduced willingness to expend effort for reward in obesity: link to adherence to a 3-month weight loss intervention. Obesity (Silver Spring) 25:1676–1681CrossRefGoogle Scholar
  20. Matsuzaki I, Takamatsu Y, Moroji T (1989) The effects of intracerebroventricularly injected corticotropin-releasing factor (CRF) on the central nervous system: behavioural and biochemical studies. Neuropeptides 13:147–155.  https://doi.org/10.1016/0143-4179(89)90085-1 CrossRefGoogle Scholar
  21. Meador-Woodruff JH, Mansour A, Bunzow JR, Van Tol HH, Watson SJ Jr, Civelli O (1989) Distribution of D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci 86:7625–7628 https://doi.org/http://www.ncbi.nlm.nih.gov/pubmed/10723008 CrossRefGoogle Scholar
  22. Nemeroff CB, Widerlöv E, Bissette G et al (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivitity in depressed patients. Science 226:1342–1344CrossRefGoogle Scholar
  23. Nowend KL, Arizzi M, Carlson BB, Salamone JD (2001) D1 or D2 antagonism in nucleus accumbens core or dorsomedial shell suppresses lever pressing for food but leads to compensatory increases in chow consumption. Pharmacol Biochem Behav 69:373–382.  https://doi.org/10.1016/S0091-3057(01)00524-X CrossRefGoogle Scholar
  24. Peciña S, Schulkin J, Berridge KC (2006) Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress? BMC Biol 4(8):8.  https://doi.org/10.1186/1741-7007-4-8 CrossRefGoogle Scholar
  25. Redgrave P, Prescott TJ, Gurney K (1999) Is the short latency dopamine burst too short to signal reinforcement error? Trends Neurosci 22:146–151.  https://doi.org/10.1016/S0166-2236(98)01373-3 CrossRefGoogle Scholar
  26. Salamone JD, Steinpreis R, McCullough L, Smith P, Grebel D, Mahan K (1991) Haloperidol and nucleus accumbens dopamine depletion suppresses lever pressing for food but increase free food consumption in a novel food-choice procedure. Psychopharmacology 104:515–521CrossRefGoogle Scholar
  27. Salamone JD, Cousins MS, Bucher S (1994) Anhedonia or anergia effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost benefit procedure. Behav Brain Res 65:221–229CrossRefGoogle Scholar
  28. Sautel F, Griffon N, Lévesque D, Pilon C, Schwartz JC, Sokoloff P (1995) A functional test identifies dopamine agonists selective for D3 versus D2 receptors. Neuroreport 6:329–332 http://www.ncbi.nlm.nih.gov/pubmed/7756621 CrossRefGoogle Scholar
  29. Shafiei N, Gray M, Viau V, Floresco SB (2012) Acute stress induces selective alterations in cost/benefit decision-making. Neuropsychopharmacology 37:2194–2209.  https://doi.org/10.1038/npp.2012.69 CrossRefGoogle Scholar
  30. Simpson EH, Winiger V, Biezonski DK, Haq I, Kandel ER, Kellendonk C (2014) Selective overexpression of dopamine D3 receptors in the striatum disrupts motivation but not cognition. Biol Psychiatry 76:823–831.  https://doi.org/10.1016/j.biopsych.2013.11.023 CrossRefGoogle Scholar
  31. Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347:146–151.  https://doi.org/10.1038/347146a0 CrossRefGoogle Scholar
  32. Sokolowski JD, Salamone JD (1998) The role of accumbens dopamine in lever pressing and response allocation: effects of 6-OHDA injected into core and dorsomedial shell. Pharmacol Biochem Behav 59:557–566CrossRefGoogle Scholar
  33. St Onge JR, Floresco SB (2009) Dopaminergic modulation of risk-based decision making. Neuropsychopharmacology 34:681–697.  https://doi.org/10.1038/npp.2008.121 CrossRefGoogle Scholar
  34. St Onge JR, Ahn S, Phillips AG, Floresco SB (2012) Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making. J Neurosci 32:16880–16891CrossRefGoogle Scholar
  35. Stopper CM, Khayambashi S, Floresco SB (2013) Receptor-specific modulation of risk-based decision making by nucleus accumbens dopamine. Neuropsychopharmacology 38:715–728.  https://doi.org/10.1038/npp.2012.240 CrossRefGoogle Scholar
  36. Treadway MT, Bossaller N, Shelton RC, Zald DH (2012) Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J Abnorm Psychol 121:553–558.  https://doi.org/10.1037/a0028813.Effort-Based CrossRefGoogle Scholar
  37. Treadway MT, Peterman JS, Zald DH, Park S (2015) Impaired effort allocation in patients with schizophrenia. Schizophr Res 161(2–3):382–385.  https://doi.org/10.1016/j.schres.2014.11.024 CrossRefGoogle Scholar
  38. Ungless MA, Singh V, Crowder TL, Yaka R, Ron D, Bonci A (2003) Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons. Neuron 39:401–407.  https://doi.org/10.1016/S0896-6273(03)00461-6 CrossRefGoogle Scholar
  39. Wanat MJ, Hopf FW, Stuber GD, Phillips PEM, Bonci A (2008) Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih. J Physiol 586(8):2157–2170.  https://doi.org/10.1113/jphysiol.2007.150078 CrossRefGoogle Scholar
  40. Wanat MJ, Bonci A, Phillips PE (2013) CRF acts in the midbrain to attenuate accumbens dopamine release to rewards but not their predictors. Nat Neurosci 16:383–385.  https://doi.org/10.1038/nn.3335 CrossRefGoogle Scholar
  41. Williams CL, Buchta WC, Riegel AC (2014) CRF-R2 and the heterosynaptic regulation of VTA glutamate during reinstatement of cocaine seeking. J Neurosci 34(31):10402–10414.  https://doi.org/10.1523/JNEUROSCI.0911-13.2014 CrossRefGoogle Scholar
  42. Winstanley CA, Zeeb FD, Bedard A, Fu K, Lai B, Steele C, Wong AC (2010) Dopaminergic modulation of the orbitofrontal cortex affects attention, motivation and impulsive responding in rats performing the five-choice serial reaction time task. Behav Brain Res 210:263–272.  https://doi.org/10.1016/j.bbr.2010.02.044 CrossRefGoogle Scholar
  43. Zapata A, Shippenberg TS (2002) D3 receptor ligands modulate extracellular dopamine clearance in the nucleus accumbens. J Neurochem 81:1035–1042.  https://doi.org/10.1046/j.1471-4159.2002.00893.x CrossRefGoogle Scholar
  44. Zapata A, Witkin JM, Shippenberg TS (2001) Selective D3 receptor agonist effects of (+)-PD 128907 on dialysate dopamine at low doses. Neuropharmacology 41:351–359.  https://doi.org/10.1016/S0028-3908(01)00069-7 CrossRefGoogle Scholar
  45. Zhang M, Balmadrid C, Kelley AE (2003) Nucleus accumbens opioid, GABAergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat. Behav Neurosci 117:202–211.  https://doi.org/10.1037/0735-7044.117.2.202 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Psychology and Djavad Mowafaghian Centre for Brain HealthUniversity of British ColumbiaVancouverCanada

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