The role of dopaminergic and serotonergic transmission in the processing of primary and monetary reward

Abstract

Natural rewards such as erotic stimuli activate common neural pathways with monetary rewards. In human studies, the manipulation of dopamine and serotonin play an important role in the processing of monetary rewards with less understood on its role on erotic stimuli. In this study, we investigate the neuromodulatory effects of dopaminergic and serotonergic transmission in the processing of erotic versus monetary visual stimuli. We scanned one hundred and two (N = 102) healthy volunteers using functional magnetic resonance imaging while performing a modified version of the well-validated monetary incentive delay task consisting of erotic, monetary and neutral visual stimuli. We show a role for enhanced central dopamine and lowered central serotonin levels in increasing activity in the right caudate and left anterior insula during anticipation of erotic relative to monetary rewards in healthy controls. We further show differential activation in the anticipation of natural versus monetary rewards with the former associated with ventromesial and dorsomesial activity and the latter with dorsal cingulate, striatal and anterior insular activity. These findings are consistent with preclinical and clinical findings of a role for dopaminergic and serotonergic mechanisms in the processing of natural rewards. Our study provides further insights into the neural substrates underlying reward processing for natural primary erotic rewards and yields importance for the neurochemical systems of addictive disorders including gambling disorder.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: The monetary incentive delay task (MID).
Fig. 2: Main effect of reward anticipation.
Fig. 3: Drug by reward interaction effect with increased erotic versus monetary anticipation in medicated groups compared to the control group in the right caudate and left anterior insula.
Fig. 4: Main effect of reward outcome.

References

  1. 1.

    Stoléru S, Fonteille V, Cornélis C, Joyal C, Moulier V. Functional neuroimaging studies of sexual arousal and orgasm in healthy men and women: a review and meta-analysis. Neurosci Biobehav Rev. 2012;36:1481–509.

    PubMed  Google Scholar 

  2. 2.

    Graf H, Malejko K, Metzger C, Walter M, Grön G, Abler B. Serotonergic, dopaminergic, and noradrenergic modulation of erotic stimulus processing in the male human brain. J Clin Med. 2019;8:363.

    CAS  PubMed Central  Google Scholar 

  3. 3.

    Graf H, Walter M, Metzger CD, Abler B. Antidepressant-related sexual dysfunction—perspectives from neuroimaging. Pharmacol Biochem Behav. 2014;121:138–45.

    CAS  PubMed  Google Scholar 

  4. 4.

    Abler B, Seeringer A, Hartmann A, Grön G, Metzger C, Walter M, et al. Neural correlates of antidepressant-related sexual dysfunction: a placebo-controlled fmri study on healthy males under subchronic paroxetine and bupropion. Neuropsychopharmacology. 2011;36:1837–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Boureau YL, Dayan P. Opponency revisited: competition and cooperation between dopamine and serotonin. Neuropsychopharmacology. 2011;36:74–97.

    CAS  PubMed  Google Scholar 

  6. 6.

    Seo D, Patrick CJ, Kennealy PJ. Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders. Aggress Violent Behav. 2008;13:383–95.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ikeda R, Igari Y, Fuchigami Y, Wada M, Kuroda N, Nakashima K. Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain. Eur J Pharm. 2011;660:318–25.

    CAS  Google Scholar 

  8. 8.

    Parsons LH, Justice JB Jr. Serotonin and dopamine sensitization in the nucleus accumbens, ventral tegmental area, and dorsal raphe nucleus following repeated cocaine administration. J Neurochem. 1993;61:1611–9.

    CAS  PubMed  Google Scholar 

  9. 9.

    Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science. 1997;275:1593–9.

    CAS  PubMed  Google Scholar 

  10. 10.

    Berridge KC, Robinson TE. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev. 1998;28:309–69.

    CAS  PubMed  Google Scholar 

  11. 11.

    Weintraub D, Koester J, Potenza MN, Siderowf AD, Stacy M, Voon V, et al. Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol. 2010;67:589–95.

    Google Scholar 

  12. 12.

    Voon V, Hassan K, Zurowski M, De Souza M, Thomsen T, Fox S, et al. Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology. 2006;67:1254–7.

    CAS  PubMed  Google Scholar 

  13. 13.

    Frohmader KS, Wiskerke J, Wise RA, Lehman MN, Coolen LM. Methamphetamine acts on subpopulations of neurons regulating sexual behavior in male rats. Neuroscience. 2010;166:771–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Volkow ND, Fowler JS, Wang GJ, Swanson JM, Telang F. Dopamine in drug abuse and addiction: Results of imaging studies and treatment implications. Arch Neurol. 2007;64:1575–9.

    PubMed  Google Scholar 

  15. 15.

    Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM. Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator. J Neurosci. 2013;33:3434–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Dossenbach M, Dyachkova Y, Pirildar S, Anders M, Khalil A, Araszkiewicz A, et al. Effects of atypical and typical antipsychotic treatments on sexual function in patients with schizophrenia: 12-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. Eur Psychiatry. 2006;21:251–8.

    PubMed  Google Scholar 

  17. 17.

    Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174:1930–3.

    PubMed  Google Scholar 

  18. 18.

    Sescousse G, Caldú X, Segura B, Dreher JC. Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies. Neurosci Biobehav Rev. 2013;37:681–96.

    PubMed  Google Scholar 

  19. 19.

    Knutson B, Greer SM. Review. Anticipatory affect: Neural correlates and consequences for choice. Philos Trans R Soc B Biol Sci. 2008;363:3771–86.

    Google Scholar 

  20. 20.

    Sescousse G, Barbalat G, Domenech P, Dreher JC. Imbalance in the sensitivity to different types of rewards in pathological gambling. Brain. 2013;136:2527–38.

    PubMed  Google Scholar 

  21. 21.

    Gola M, Wordecha M, Sescousse G, Lew-Starowicz M, Kossowski B, Wypych M, et al. Can pornography be addictive? An fMRI study of men seeking treatment for problematic pornography use. Neuropsychopharmacology. 2017;42:2021–31.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Young S. Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects. J Psychiatry Neurosci. 2013;38:294–305.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Grove JR, Prapavessis H. Preliminary evidence for the reliability and validity of an abbreviated profile of mood states. Int J Sport Psychol. 1992;23:93–109.

    Google Scholar 

  24. 24.

    Dozois DJA. Beck Depression Inventory-II. Corsini Encycl Psychol. 2010;78:490–8.

    Google Scholar 

  25. 25.

    Spielberger CD. State-trait anxiety inventory for adults. 1983.

  26. 26.

    Wechsler D. Wechsler adult intelligence scale–Fourth Edition (WAIS–IV). San Antonio, TX: Psychol Corp; 2014.

  27. 27.

    Nelson HE, Willison J. National Adult Reading Test (NART) NFER. vol. UK: NFER-N; 1991.

  28. 28.

    Rutledge RB, Skandali N, Dayan P, Dolan RJ. Dopaminergic modulation of decision making and subjective well-being. J Neurosci. 2015;35:9811–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Worbe Y, Palminteri S, Savulich G, Daw ND, Fernandez-Egea E, Robbins TW, et al. Valence-dependent influence of serotonin depletion on model-based choice strategy. Mol Psychiatry. 2016;21:624–9.

    CAS  PubMed  Google Scholar 

  30. 30.

    Penny WD, Friston KJ, Ashburner JT, Kiebel SJ, Nichols TE, editors. Statistical parametric mapping: the analysis of functional brain images. Elsevier; 2011.

  31. 31.

    Calhoun VD, Wager TD, Krishnan A, Rosch KS, Seymour KE, Nebel MB, et al. The impact of T1 versus EPI spatial normalization templates for fMRI data analyses. Hum Brain Mapp. 2017;38:5331–42.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Greenwald AG, Nosek BA, Banaji MR. Understanding and using the Implicit Association Test: I. an improved scoring algorithm. J Pers Soc Psychol. 2003;85:197–216.

    PubMed  Google Scholar 

  33. 33.

    Kennerley SW, Walton ME. Decision making and reward in frontal cortex: Complementary evidence from neurophysiological and neuropsychological studies. Behav Neurosci. 2011;125:297–317.

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Botvinick MM, Cohen JD, Carter CS. Conflict monitoring and anterior cingulate cortex: an update. Trends Cogn Sci. 2004;8:539–46.

    Google Scholar 

  35. 35.

    Kolling N, Behrens TEJ, Mars RB, Rushworth MFS. Neural mechanisms of foraging. Science. 2012;335:95–98.

    Google Scholar 

  36. 36.

    Boorman ED, Rushworth MF, Behrens TE. Ventromedial prefrontal and anterior cingulate cortex adopt choice and default reference frames during sequential multi-alternative choice. J Neurosci. 2013;33:2242–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Georgiadis JR, Kringelbach ML. The human sexual response cycle: brain imaging evidence linking sex to other pleasures. Prog Neurobiol. 2012;98:49–81.

    CAS  PubMed  Google Scholar 

  38. 38.

    Guillem K, Brenot V, Durand A, Ahmed SH. Neuronal representation of individual heroin choices in the orbitofrontal cortex. Addict Biol. 2018;23:880–8.

    PubMed  Google Scholar 

  39. 39.

    Schoenbaum G, Chiba AA, Gallagher M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning. Nat Neurosci. 1998;1:155–9.

    CAS  PubMed  Google Scholar 

  40. 40.

    Krueger CE, Laluz V, Rosen HJ, Neuhaus JM, Miller BL, Kramer JH. Double dissociation in the anatomy of socioemotional disinhibition and executive functioning in dementia. Neuropsychology. 2011;25:249.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Deng W, Rolls ET, Ji X, Robbins TW, Banaschewski T, Bokde ALW, et al. Separate neural systems for behavioral change and for emotional responses to failure during behavioral inhibition. Hum Brain Mapp. 2017;38:3527–37.

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Voon V, Napier TC, Frank MJ, Sgambato-Faure V, Grace AA, Rodriguez-Oroz M, et al. Impulse control disorders and levodopa-induced dyskinesias in Parkinson’s disease: an update. Lancet Neurol. 2017;16:238–50.

    PubMed  Google Scholar 

  43. 43.

    Politis M, Loane C, Wu K, O’Sullivan SS, Woodhead Z, Kiferle L, et al. Neural response to visual sexual cues in dopamine treatment-linked hypersexuality in Parkinson’s disease. Brain. 2013;136:400–11.

    PubMed  Google Scholar 

  44. 44.

    Voon V, Mole TB, Banca P, Porter L, Morris L, Mitchell S, et al. Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours. PLoS ONE. 2014;9.

  45. 45.

    Mechelmans DJ, Irvine M, Banca P, Porter L, Mitchell S, Mole TB, et al. Enhanced attentional bias towards sexually explicit cues in individuals with and without compulsive sexual behaviours. PLoS ONE. 2014;9:8.

    Google Scholar 

  46. 46.

    Borsini F. KR Evans - US Patent 7 151,103, 2006 undefined. Method of treating female hypoactive sexual desire disorder with flibanserin. Google Patents. 2006.

  47. 47.

    Lenoir M, Serre F, Cantin L, Ahmed SH. Intense sweetness surpasses cocaine reward. PLoS ONE 2007;2:e698.

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Mahler SV, Smith KS, Berridge KC. Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’ of a sweet reward. Neuropsychopharmacology. 2007;32:2267–78.

    CAS  PubMed  Google Scholar 

  49. 49.

    Cheer JF, Wassum KM, Heien MLAV, Phillips PEM, Wightman RM. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci. 2004;24:4393–4400.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Peciña S, Cagniard B, Berridge KC, Aldridge JW, Zhuang X. Hyperdopaminergic mutant mice have higher ‘wanting’ but not ‘liking’ for sweet rewards. J Neurosci. 2003;23:9395–402.

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    McCabe C, Huber A, Harmer CJ, Cowen PJ. The D2 antagonist sulpiride modulates the neural processing of both rewarding and aversive stimuli in healthy volunteers. Psychopharmacology. 2011;217:271–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    O’Doherty J, Rolls ET, Francis S, Bowtell R, McGlone F. Representation of pleasant and aversive taste in the human brain. J Neurophysiol. 2001;85:1315–21.

    PubMed  Google Scholar 

  53. 53.

    Knutson B, Adams CM, Fong GW, Hommer D. Anticipation of increasing monetary reward selectively recruits nucleus accumbens. J Neurosci. 2001;21:RC159.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Brand M, Snagowski J, Laier C, Maderwald S. Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction. Neuroimage. 2016;129:224–32.

    PubMed  Google Scholar 

  55. 55.

    Duvauchelle CL, Levitin M, MacConell LA, Lee LK, Ettenberg A. Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward. Brain Res. 1992;576:104–10.

    CAS  PubMed  Google Scholar 

  56. 56.

    Diekhof EK, Gruber O. When desire collides with reason: functional interactions between anteroventral prefrontal cortex and nucleus accumbens underlie the human ability to resist impulsive desires. J Neurosci. 2010;30:1488–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Grant JE, Kim SW, Potenza MN, Blanco C, Ibanez A, Stevens L, et al. Paroxetine treatment of pathological gambling: a multi-centre randomized controlled trial. Int Clin Psychopharmacol. 2003;18:243–9.

    PubMed  Google Scholar 

  58. 58.

    Gola M, Potenza MN. Paroxetine treatment of problematic pornography use: a case series. J Behav Addict. 2016;5:529–32.

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    DeRogatis LR, Komer L, Katz M, Moreau M, Kimura T, Garcia M Jr, et al. Treatment of hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the VIOLET Study. J Sex Med. 2012;9:1074–85.

    CAS  PubMed  Google Scholar 

  60. 60.

    Caruso S, Agnello C, Intelisano G, Farina M, Di Mari L, Cianci A. Placebo-controlled study on efficacy and safety of daily apomorphine SL intake in premenopausal women affected by hypoactive sexual desire disorder and sexual arousal disorder. Urology. 2004;63:955–9.

    PubMed  Google Scholar 

  61. 61.

    Masand PS, Ashton AK, Gupta S, Frank B. Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study. Am J Psychiatry. 2001;158:805–7.

    CAS  PubMed  Google Scholar 

  62. 62.

    Yee A, Loh HS, Ong TA, Ng CG, Sulaiman AH. Randomized, double-blind, parallel-group, placebo-controlled trial of bupropion as treatment for methadone-emergent sexual dysfunction in men. Am J Mens Health. 2018;12:1705–18.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

Each author’s contributions are listed in the author order using initials to indicate their contributions to study design (1); or the acquisition (2), analysis (3), or interpretation of data for the work (4); and in drafting the work or revising it critically for important intellectual content (5); and final approval of the version to be published (6): CS: 1–6 NS: 4–6 CG: 1,3,6 TK; 2–3,6 HS: 2-3,6 KF: 2,6, AM: 1–2,4-6 VV: 1–6.

Corresponding author

Correspondence to Valerie Voon.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Schmidt, C., Skandali, N., Gleesborg, C. et al. The role of dopaminergic and serotonergic transmission in the processing of primary and monetary reward. Neuropsychopharmacol. 45, 1490–1497 (2020). https://doi.org/10.1038/s41386-020-0702-3

Download citation