Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-05T04:04:44.545Z Has data issue: false hasContentIssue false
  • English
  • Français

Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment

Published online by Cambridge University Press:  18 May 2016

Z. Dean ,
S. Horndasch ,
P. Giannopoulos  and
C. McCabe
Z. Dean
Affiliation:
School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
S. Horndasch
Affiliation:
School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
P. Giannopoulos
Affiliation:
School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
C. McCabe*
Affiliation:
School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
*
*Address for correspondence: Dr C. McCabe, Lecturer in Neuroscience, School of Psychology and Clinical Language Sciences, University of Reading, Reading RG6 6AL, UK. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear.

Method

Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes.

Results

Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase.

Conclusions

Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect.

Keywords

Rewardbrainbupropiondopaminedepressionaversion
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 11 , August 2016 , pp. 2263 - 2274
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abler, B, Seeringer, A, Hartmann, A, Gron, G, Metzger, C, Walter, M, Stingl, J (2011). Neural correlates of antidepressant-related sexual dysfunction: a placebo-controlled fMRI study on healthy males under subchronic paroxetine and bupropion. Neuropsychopharmacology 36, 1837–1847.Google Scholar
Argyropoulos, SV, Nutt, DJ (2013). Anhedonia revisited: is there a role for dopamine-targeting drugs for depression? Journal of Psychopharmacology 27, 869–877.Google Scholar
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives General Psychiatry 4, 561–571.Google Scholar
Berridge, KC (2007). The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology 191, 391–431.CrossRefGoogle ScholarPubMed
Berridge, KC, Kringelbach, ML (2008). Affective neuroscience of pleasure: reward in humans and animals. Psychopharmacology 199, 457–480.CrossRefGoogle ScholarPubMed
Berridge, KC, Robinson, TE, Aldridge, JW (2009). Dissecting components of reward: ‘liking’, ‘wanting’, and learning. Current Opinion in Pharmacology 9, 65–73.Google Scholar
Bylsma, LM, Morris, BH, Rottenberg, J (2008). A meta-analysis of emotional reactivity in major depressive disorder. Clinical Psychology Review 28, 676–691.Google Scholar
Carver, CS, White, TL (1994). Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. Journal of Personality and Social Psychology 67, 319.Google Scholar
Collins, DL, Neelin, P, Peters, TM, Evans, AC (1994). Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. Journal of Computer Assisted Tomography 18, 192–205.Google Scholar
Corcoran, C, Wong, ML, O'Keane, V (2004). Bupropion in the management of apathy. Journal of Psychopharmacology 18, 133–135.Google Scholar
Dayan, P, Balleine, BW (2002). Reward, motivation, and reinforcement learning. Neuron 36, 285–298.Google Scholar
De Araujo, IE, Kringelbach, ML, Rolls, ET, Hobden, P (2003). Representation of umami taste in the human brain. Journal of Neurophysiology 90, 313–319.CrossRefGoogle ScholarPubMed
Delgado, MR, Jou, RL, Ledoux, JE, Phelps, EA (2009). Avoiding negative outcomes: tracking the mechanisms of avoidance learning in humans during fear conditioning. Frontiers in Behavioral Neuroscience 3, 33.CrossRefGoogle ScholarPubMed
Dunlop, BW, Nemeroff, CB (2007). The role of dopamine in the pathophysiology of depression. Archives of General Psychiatry 64, 327–337.Google Scholar
Dwoskin, LP, Rauhut, AS, King-Pospisil, KA, Bardo, MT (2006). Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent. CNS Drug Reviews 12, 178–207.Google Scholar
Epstein, J, Pan, H, Kocsis, JH, Yang, Y, Butler, T, Chusid, J, Hochberg, H, Murrough, J, Strohmayer, E, Stern, E, Silbersweig, DA (2006). Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. American Journal of Psychiatry 163, 1784–1790.CrossRefGoogle ScholarPubMed
Fawcett, J, Clark, DC, Scheftner, WA, Gibbons, RD (1983). Assessing anhedonia in psychiatric patients. Archives of General Psychiatry 40, 79–84.Google Scholar
Forbes, EE, Hariri, AR, Martin, SL, Silk, JS, Moyles, DL, Fisher, PM, Brown, SM, Ryan, ND, Birmaher, B, Axelson, DA, Dahl, RE (2009). Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. American Journal of Psychiatry 166, 64–73.Google Scholar
Frey, LA, Malinowska, L, Harley, K, Salhi, L, Iqbal, S, Sharma, S, McCabe, C (2015). Investigating subtypes of reward processing deficits as trait markers for depression. Translational Developmental Psychiatry 3, 27517. http://dx.doi.org/10.3402/tdp.v3.2751 Google Scholar
Friston, KJ, Glaser, DE, Henson, RN, Kiebel, S, Phillips, C, Ashburner, J (2002). Classical and Bayesian inference in neuroimaging: applications. Neuroimage 16, 484–512.Google Scholar
Friston, KJ, Worsley, KJ, Frackowiak, RSJ, Mazziotta, JC, Evans, AC (1994). Assessing the significance of focal activations using their spatial extent. Human Brain Mapping 1, 214–220.Google Scholar
Gard, DE, Kring, AM, Gard, MG, Horan, WP, Green, MF (2007). Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophrenia Research 93, 253–260.Google Scholar
Garner, DM, Olmsted, MP, Bohr, Y, Garfinkel, PE (1982). The eating attitudes test: psychometric features and clinical correlates. Psychological Medicine 12, 871–878.Google Scholar
Gerdes, AB, Wieser, MJ, Mühlberger, A, Weyers, P, Alpers, GW, Plichta, MM, Breuer, F, Pauli, P (2010). Brain activations to emotional pictures are differentially associated with valence and arousal ratings. Frontiers in Human Neuroscience 4, 175.Google Scholar
Harmer, CJ, Goodwin, GM, Cowen, PJ (2009). Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. British Journal of Psychiatry 195, 102–108.CrossRefGoogle Scholar
Horder, J, Harmer, CJ, Cowen, PJ, McCabe, C (2010). Reduced neural response to reward following 7 days treatment with the cannabinoid CB(1) antagonist rimonabant in healthy volunteers. International Journal of Neuropsychopharmacology 13, 1103–1113.Google Scholar
Kerr, DL, McLaren, DG, Mathy, RM, Nitschke, JB (2012). Controllability modulates the anticipatory response in the human ventromedial prefrontal cortex. Frontiers in Psychology 3, 557. doi: 10.3389/fpsyg.2012.00557.Google Scholar
Kim, H, Shimojo, S, O'Doherty, JP (2011). Overlapping responses for the expectation of juice and money rewards in human ventromedial prefrontal cortex. Cerebral Cortex 21, 769–776.Google Scholar
Knutson, B, Bhanji, JP, Cooney, RE, Atlas, LY, Gotlib, IH (2008). Neural responses to monetary incentives in major depression. Biological Psychiatry 63, 686–692.Google Scholar
Knutson, B, Greer, SM (2008). Anticipatory affect: neural correlates and consequences for choice. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 363, 3771–3786.CrossRefGoogle ScholarPubMed
Kringelbach, ML, Berridge, KC (2010). The functional neuroanatomy of pleasure and happiness. Discovery Medicine 9, 579–587.Google Scholar
Kumar, P, Waiter, G, Ahearn, T, Milders, M, Reid, I, Steele, JD (2008). Abnormal temporal difference reward-learning signals in major depression. Brain 131, 2084–2093.Google Scholar
Liljeholm, M, O'Doherty, JP (2012). Contributions of the striatum to learning, motivation, and performance: an associative account. Trends in Cognitive Sciences 16, 467–475.CrossRefGoogle ScholarPubMed
Luking, KR, Neiman, JS, Luby, JL, Barch, DM (2015). Reduced hedonic capacity/approach motivation relates to blunted responsivity to gain and loss feedback in children. Journal of Clinical Child & Adolescent Psychology 1–13.Google ScholarPubMed
McCabe, C (2014). Neural correlates of anhedonia as a trait marker for depression. In Anhedonia: A Comprehensive Handbook, Volume II (ed. Ritsner, M.), pp. 159–174. Springer Science+Business Media Dordrecht. ISBN 9787401768096.Google Scholar
McCabe, C, Cowen, PJ, Harmer, CJ (2009). Neural representation of reward in recovered depressed patients. Psychopharmacology (Berlin) 205, 667–677.Google Scholar
McCabe, C, Mishor, Z, Cowen, PJ, Harmer, CJ (2010). Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment. Biological Psychiatry 67, 439–445.Google Scholar
Nutt, D, Demyttenaere, K, Janka, Z, Aarre, T, Bourin, M, Canonico, PL, Carrasco, JL, Stahl, S (2007). The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. Journal of Psychopharmacology 21, 461–471.Google Scholar
O'Doherty, J, Rolls, ET, Francis, S, Bowtell, R, McGlone, F (2001). Representation of pleasant and aversive taste in the human brain. Journal of Neurophysiology 85, 1315–1321.Google Scholar
Opbroek, A, Delgado, PL, Laukes, C, McGahuey, C, Katsanis, J, Moreno, FA, Manber, R (2002). Emotional blunting associated with SSRI-induced sexual dysfunction. Do SSRIs inhibit emotional responses? International Journal of Neuropsychopharmacology 5, 147–151.Google Scholar
Peciña, S (2008). Opioid reward ‘liking'and ‘wanting'in the nucleus accumbens. Physiology & Behavior 94, 675–680.CrossRefGoogle ScholarPubMed
Peciña, S, Berridge, KC (2005). Hedonic hot spot in nucleus accumbens shell: where do μ-opioids cause increased hedonic impact of sweetness? Journal of Neuroscience 25, 11777–11786.Google Scholar
Peciña, S, Smith, KS, Berridge, KC (2006). Hedonic hot spots in the brain. The Neuroscientist 12, 500–511.Google Scholar
Pereira, VM, Arias-Carrión, O, Machado, S, Nardi, AE, Silva, AC (2014). Bupropion in the depression-related sexual dysfunction: a systematic review. CNS & Neurological Disorders – Drug Targets 13, 1079–1088.Google Scholar
Peters, J, Buchel, C (2010). Neural representations of subjective reward value. Behavioral Brain Res 213, 135–141.Google Scholar
Pizzagalli, DA, Holmes, AJ, Dillon, DG, Goetz, EL, Birk, JL, Bogdan, R, Dougherty, DD, Iosifescu, DV, Rauch, SL, Fava, M (2009). Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. American Journal of Psychiatry 166, 702–710.Google Scholar
Price, J, Cole, V, Goodwin, GM (2009). Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. British Journal of Psychiatry 195, 211–217.Google Scholar
Price, J, Drevets, WC (2009). Neurocircuitry of mood disorders. Neuropsychopharmacology Review 35, 192–216.Google Scholar
Rolls, ET, McCabe, C (2007). Enhanced affective brain representations of chocolate in cravers vs. non-cravers. European Journal of Neuroscience 26, 1067–1076.Google Scholar
Rottenberg, J (2007). Major depressive disorder: emerging evidence for emotion context insensitivity. In Emotion and Psychopathology: Bridging Affective and Clinical Science (ed. J. Rottenberg and S.L. Johnson), pp. 151–165. American Psychological Association: Washington, DC.Google Scholar
Rottenberg, J, Gross, JJ, Gotlib, IH (2005). Emotion context insensitivity in major depressive disorder. Journal of Abnormal Psychology 114, 627–639.Google Scholar
Scholl, J, Kolling, N, Nelissen, N, Wittmann, MK, Harmer, CJ, Rushworth, MF (2015). The good, the Bad, and the irrelevant: neural mechanisms of learning real and hypothetical rewards and effort. Journal of Neuroscience 35, 11233–11251.Google Scholar
Scott, TR, Edwards, EM, Smith, CA, Hilgert, KG, Schwartz, GJ, Pritchard, TC (2005). Medial orbitofrontal cortex: its role in mediating satiety in the macaque. Chemical Senses 30, i190.Google Scholar
Sescousse, G, Caldú, X, Segura, B, Dreher, J-C (2013). Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies. Neuroscience & Biobehavioral Reviews 37, 681–696.Google Scholar
Sheline, YI, Barch, DM, Donnelly, JM, Ollinger, JM, Snyder, AZ, Mintun, MA (2001). Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biological Psychiatry 50, 651–658.Google Scholar
Shelton, RC, Tomarken, AJ (2001). Can recovery from depression be achieved? Psychiatric Services 52, 1469–1478.Google Scholar
Sherdell, L, Waugh, CE, Gotlib, IH (2012). Anticipatory pleasure predicts motivation for reward in major depression. Journal of Abnormal Psychology 121, 51–60.Google Scholar
Smith, KS, Berridge, KC (2005). The ventral pallidum and hedonic reward: neurochemical maps of sucrose ‘liking’ and food intake. Journal of Neuroscience 25, 8637–8649.Google Scholar
Smoski, MJ, Felder, J, Bizzell, J, Green, SR, Ernst, M, Lynch, TR, Dichter, GS (2009). fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder. Journal of Affective Disorders 118, 69–78.Google Scholar
Snaith, RP, Hamilton, M, Morley, S, Humayan, A, Hargreaves, D, Trigwell, P (1995). A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. British Journal of Psychiatry 167, 99–103.Google Scholar
Spijker, J, Bijl, RV, de Graaf, R, Nolen, WA (2001). Determinants of poor 1-year outcome of DSM-III-R major depression in the general population: results of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Acta Psychiatrica Scandinavica 103, 122–130.Google Scholar
Spitzer, RL, Williams, JB, Gibbon, M, First, MB (1992). The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Archives of General Psychiatry 49, 624–629.Google Scholar
Stahl, SM, Pradko, JF, Haight, BR, Modell, JG, Rockett, CB, Learned-Coughlin, S (2004). A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Primary Care Companion to the Journal of Clinical Psychiatry 6, 159.Google Scholar
Surguladze, SA, Young, AW, Senior, C, Brebion, G, Travis, MJ, Phillips, ML (2004). Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression. Neuropsychology 18, 212–218.Google Scholar
Treadway, MT, Bossaller, NA, Shelton, RC, Zald, DH (2012). Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. Journal of Abnormal Psychology 121, 553–558.Google Scholar
Treadway, MT, Zald, DH (2011). Reconsidering anhedonia in depression: lessons from translational neuroscience. Neuroscience & Biobehavioral Reviews 35, 537–555.Google Scholar
Tudge, L, Williams, C, Cowen, PJ, McCabe, C (2015). Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers. International Journal of Neuropsychopharmacology 18(6). pii: pyu094. doi: 10.1093/ijnp/pyu094.Google Scholar
Ubl, B, Kuehner, C, Kirsch, P, Ruttorf, M, Diener, C, Flor, H (2015). Altered neural reward and loss processing and prediction error signalling in depression. Social Cognitive and Affective Neuroscience 10, 1102–1112.Google Scholar
Von Zerssen, D, Strian, F, Schwarz, D (1974). Evaluation of depressive states, especially in longitudinal studies. Modern Problems of Pharmacopsychiatry 7, 189–202.Google Scholar
Wheeler, RA, Carelli, RM (2006). The neuroscience of pleasure. Focus on ‘Ventral pallidum firing codes hedonic reward: when a bad taste turns good’. Journal of Neurophysiology 96, 2175–2176.Google Scholar
Wiers, CE, Stelzel, C, Park, SQ, Gawron, CK, Ludwig, VU, Gutwinski, S, Heinz, A, Lindenmeyer, J, Wiers, RW, Walter, H (2014). Neural correlates of alcohol-approach bias in alcohol addiction: the spirit is willing but the flesh is weak for spirits. Neuropsychopharmacology 39, 688–697.Google Scholar
Wilson, JL, Jenkinson, M, de Araujo, I, Kringelbach, ML, Rolls, ET, Jezzard, P (2002). Fast, fully automated global and local magnetic field optimization for fMRI of the human brain. Neuroimage 17, 967–976.Google Scholar
Worsley, KJ, Marrett, P, Neelin, AC, Friston, KJ, Evans, AC (1996). A unified statistical approach for determining significant signals in images of cerebral activation. Human Brain Mapping 4, 58–73.Google Scholar
Yang, XH, Huang, J, Zhu, CY, Wang, YF, Cheung, EF, Chan, RC, Xie, GR (2014). Motivational deficits in effort-based decision making in individuals with subsyndromal depression, first-episode and remitted depression patients. Psychiatry Research 220, 874–882.CrossRefGoogle ScholarPubMed
Zhang, W-N, Chang, S-H, Guo, L-Y, Zhang, K-L, Wang, J (2013). The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies. Journal of Affective Disorders 151, 531–539.Google Scholar
Zisook, S, Rush, AJ, Haight, BR, Clines, DC, Rockett, CB (2006). Use of bupropion in combination with serotonin reuptake inhibitors. Biological Psychiatry 59, 203–210.Google Scholar
Supplementary material: File

Dean supplementary material

Figures S1-S4 and Tables S1-S3

Download Dean supplementary material(File)
File 529.4 KB