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.
Subscribe to Journal
Get full journal access for 1 year
only $43.69 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
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.
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.
Graf H, Walter M, Metzger CD, Abler B. Antidepressant-related sexual dysfunction—perspectives from neuroimaging. Pharmacol Biochem Behav. 2014;121:138–45.
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.
Boureau YL, Dayan P. Opponency revisited: competition and cooperation between dopamine and serotonin. Neuropsychopharmacology. 2011;36:74–97.
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.
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.
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.
Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science. 1997;275:1593–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Knutson B, Greer SM. Review. Anticipatory affect: Neural correlates and consequences for choice. Philos Trans R Soc B Biol Sci. 2008;363:3771–86.
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.
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.
Young S. Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects. J Psychiatry Neurosci. 2013;38:294–305.
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.
Dozois DJA. Beck Depression Inventory-II. Corsini Encycl Psychol. 2010;78:490–8.
Spielberger CD. State-trait anxiety inventory for adults. 1983.
Wechsler D. Wechsler adult intelligence scale–Fourth Edition (WAIS–IV). San Antonio, TX: Psychol Corp; 2014.
Nelson HE, Willison J. National Adult Reading Test (NART) NFER. vol. UK: NFER-N; 1991.
Rutledge RB, Skandali N, Dayan P, Dolan RJ. Dopaminergic modulation of decision making and subjective well-being. J Neurosci. 2015;35:9811–22.
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.
Penny WD, Friston KJ, Ashburner JT, Kiebel SJ, Nichols TE, editors. Statistical parametric mapping: the analysis of functional brain images. Elsevier; 2011.
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.
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.
Kennerley SW, Walton ME. Decision making and reward in frontal cortex: Complementary evidence from neurophysiological and neuropsychological studies. Behav Neurosci. 2011;125:297–317.
Botvinick MM, Cohen JD, Carter CS. Conflict monitoring and anterior cingulate cortex: an update. Trends Cogn Sci. 2004;8:539–46.
Kolling N, Behrens TEJ, Mars RB, Rushworth MFS. Neural mechanisms of foraging. Science. 2012;335:95–98.
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.
Georgiadis JR, Kringelbach ML. The human sexual response cycle: brain imaging evidence linking sex to other pleasures. Prog Neurobiol. 2012;98:49–81.
Guillem K, Brenot V, Durand A, Ahmed SH. Neuronal representation of individual heroin choices in the orbitofrontal cortex. Addict Biol. 2018;23:880–8.
Schoenbaum G, Chiba AA, Gallagher M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning. Nat Neurosci. 1998;1:155–9.
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.
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.
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.
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.
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.
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.
Borsini F. KR Evans - US Patent 7 151,103, 2006 undefined. Method of treating female hypoactive sexual desire disorder with flibanserin. Google Patents. 2006.
Lenoir M, Serre F, Cantin L, Ahmed SH. Intense sweetness surpasses cocaine reward. PLoS ONE 2007;2:e698.
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.
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.
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.
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.
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.
Knutson B, Adams CM, Fong GW, Hommer D. Anticipation of increasing monetary reward selectively recruits nucleus accumbens. J Neurosci. 2001;21:RC159.
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.
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.
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.
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.
Gola M, Potenza MN. Paroxetine treatment of problematic pornography use: a case series. J Behav Addict. 2016;5:529–32.
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.
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.
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.
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.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
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