Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans
Yulia Worbe, George Savulich, Sanne de Wit, Emilio Fernandez-Egea, Trevor W Robbins, Yulia Worbe, George Savulich, Sanne de Wit, Emilio Fernandez-Egea, Trevor W Robbins
Abstract
Background: Optimal behavioral performance results from a balance between goal-directed and habitual systems of behavioral control, which are modulated by ascending monoaminergic projections. While the role of the dopaminergic system in behavioral control has been recently addressed, the extent to which changes in global serotonin neurotransmission could influence these 2 systems is still poorly understood.
Methods: We employed the dietary acute tryptophan depletion procedure to reduce serotonin neurotransmission in 18 healthy volunteers and 18 matched controls. We used a 3-stage instrumental learning paradigm that includes an initial instrumental learning stage, a subsequent outcome-devaluation test, and a slip-of-action stage, which directly tests the balance between hypothetical goal-directed and habitual systems. We also employed a separate response inhibition control test to assess the behavioral specificity of the results.
Results: Acute tryptophan depletion produced a shift of behavioral performance towards habitual responding as indexed by performance on the slip-of-action test. Moreover, greater habitual responding in the acute tryptophan depletion group was predicted by a steeper decline in plasma tryptophan levels. In contrast, acute tryptophan depletion left intact the ability to use discriminative stimuli to guide instrumental choice as indexed by the instrumental learning stage and did not impair inhibitory response control.
Conclusions: The major implication of this study is that serotonin modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. Our findings thus imply that diminished serotonin neurotransmission shifts behavioral control towards habitual responding.
Keywords: 5-HT; goal-directed behavior; inhibitory control; serotonin; stimulus-response habit learning; tryptophan depletion.
© The Author 2015. Published by Oxford University Press on behalf of CINP.
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References
- Ardis TC, Cahir M, Elliott JJ, Bell R, Reynolds GP, Cooper SJ. (2009) Effect of acute tryptophan depletion on noradrenaline and dopamine in the rat brain. J Psychopharmacol 23:51–55.
- Balleine BW, O’Doherty JP. (2010) Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology 35:48–69.
- Bayer J, Bandurski P, Sommer T. (2013) Differential modulation of activity related to the anticipation of monetary gains and losses across the menstrual cycle. Euro J Neurosci 38:3519–3526.
- Beck AT, Steer RA, Ball R, Ranieri W. (1996) Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Personal Assess 67:588–597.
- Biggio G, Fadda F, Fanni P, Tagliamonte A, Gessa GL. (1974) Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci 14:1321–1329.
- Boureau YL, Dayan P. (2011) Opponency revisited: competition and cooperation between dopamine and serotonin. Neuropsychopharmacology 36:74–97.
- Bright P, Jaldow E, Kopelman MD. (2002) The National Adult Reading Test as a measure of premorbid intelligence: a comparison with stimates derived from demographic variables. J Int Neuropsychol Soc 8:847–854.
- Carpenter LL, Anderson GM, Pelton GH, Gudin JA, Kirwin PD, Price LH, Heninger GR, McDougle CJ. (1998) Tryptophan depletion during continuous CSF sampling in healthy human subjects. Neuropsychopharmacology 19:26–35.
- Cillan CM, Robbins TW. (2014) Goal-directed learning and obsessive–compulsive disorders. Philos Trans R Soc Lond B Biol Sci 369.
- Clark L, Roiser JP, Cools R, Rubinsztein DC, Sahakian BJ, Robbins TW. (2005) Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity. Psychopharmacology 182:570–578.
- Clarke H, Dalley J, Crofts H, Robbins T, Roberts A. (2004) Cognitive inflexibility after prefrontal serotonin depletion. Science 304:878–880.
- Cools R, Roberts AC, Robbins TW. (2008) Serotoninergic regulation of emotional and behavioral control processes. Trends Cogn Sci 12:31–40.
- Cools R, Nakamura K, Daw ND. (2011) Serotonin and dopamine: unifying affective, activational, and decision functions. Neuropsychopharmacology 36:98–113.
- Cox SM, Benkelfat C, Dagher A, Delaney JS, Durand F, Kolivakis T, Casey KF, Leyton M. (2011) Effects of lowerd serotonin transmission on cocaine-induced striatal dopamine response: PET (11C)raclopride study in humans. Br J Psychiatry 199:391–397.
- Crockett MJ, Clark L, Apergis-Schoute AM, Morein-Zamir S, Robbins TW. (2012a) Serotoninmodulates the effects of Pavlovian aversive predictions on response vigor. Neuropsychopharmacology 37.
- Crockett MJ, Clark L, Roiser JP, Robinson OJ, Cools R, Chase HW, Ouden H, Apergis-Schoute A, Campbell-Meiklejohn D, Seymour B, Sahakian BJ, Rogers RD, Robbins TW. (2012b) Converging evidence for central 5-HT effects in acute tryptophan depletion. Mol Psychiatry 17:121–123.
- Dayan P, Huys QJ. (2009) Serotonin in affective control. Annu Rev Neurosci 32:95–126.
- de Wit S, Niry D, Wariyar R, Aitken MRF, Dickinson A. (2007) Stimulus–outcome interactions during conditional discrimination learning by rats and humans. J Exp Psycholol Anim Behav Process 33:1–11.
- de Wit S, Corlett PR, Aitken MRF, Dickinson A, Fletcher PC. (2009) Differential engagement of the ventromedial prefrontal cortex by goal-directed and habitial behavior towards food pictures in humans. J Neurosci 29:11330–11338.
- de Wit S, Watson P, Harsay HA, Cohen MX, van de Vijver I, Ridderinkhof RK. (2012a) Corticostriatal connectivity underlies individual differences in the balance between habitual and goal-directed action control. J Neurosci 32:12066–12075.
- de Wit S, Standing HR, Devito EE, Robinson OJ, Ridderinkhof KR, Robbins TW, Sahakian BJ. (2012b) Reliance on habits at the expense of goal-directed control following dopamine precursor depletion. Psychopharmacology (Berl) 219:621–631.
- Dickinson A. (1985) Actions and habits: the development of behavioral and autonomy. Philos Trans R Soc Lond B Biol Sci 308.
- Eagle DM, Bari A, Robbins TW. (2008) The neuropsychoparmacology of action inhibition: cross-species translation of the stop-signal and go-no go task. Psychopharmacology 199:439–456.
- Eagle DM, Lehmann O, Theobald DE, Pena Y, Zakaria R, Ghosh R, Dalley JW, Robbins TW. (2009) Serotonin depletion impairs waiting but not stop-signal reaction time in rats: implications for theories of the role of 5-HT in behavioral inhibition. Neuropsychopharmacology 34:1311–1321.
- Eskenazi D, Neumaier JF. (2011) Increased expression of 5-HT(6) receptors in dorsolateral striatum decreases habitual lever pressing, but do not affect learning aquisition of simple operant task in rats. Euro J Neurosci 34:343–351.
- Everitt BJ, Robbins TW. (2005a) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489.
- Everitt BJ, Robbins TW. (2005b) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neuroscience 8:1481–1489.
- Faure A, Haberland U, Conde F, El Massioui N. (2005) Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation. J Neurosci 25:2771–2780.
- Gillan CM, Papmeyer M, Morein-Zamir S, Sahakian BJ, Fineberg NA, Robbins TW, de Wit S. (2011) Disruption in the balance between goal-directed behavior and habit learning in obsessive-compulsive disorder. Am J Psychiatry 168:718–726.
- Graybiel AM. (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359–387.
- Hampson E, Morley EE. (2013) Estradiol concentrations and working memory performance in women of reproductive age. Psychoneuroendocrinology 38:2897–2904.
- Hsieh P, Chen K, Yeh T, Lee I, Chen P, Yao W, Chui C, Chen C, Liao M, Yang Y. (2014) Lower avalability of midbrain serotonin transporter between healthy subjects with and without a family history of major depressive disorder - a preliminary two ligand SPECT study. Eur Psychiatry 29:414–418.
- Lingawi NW, Balleine BW. (2012) Amygdala central nucleus interacts with dosolateral striatum to regulate the aquisition of habits. J Neurosci 32:1073–1081.
- Marazziti D, Baroni S, Pirone A, Giannaccini G, Betti L, Schmid L, Vatteroni E, Palego L, Borsini F, Bordi F, Piano I, Gargini C, Castagna M, Catena-Dell’osso M, Lucacchini A. (2012) Distribution of serotonin receptor of type 6 (5-HT6) in human brain post-mortem. A pharmacology, autoradiography and immunohistochemistry study. Neurochem Res 37:920–927.
- Nelson A, Killcross S. (2006) Amphetamine exposure enhances habit formation. J Neurosci 26:3805–3812.
- Nelson AD, Killcross S. (2012) Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists. Front Neurosi 2013:76.
- O’Callaghan C, Moustafa AA, de Wit S, Shine JM, Robbins TW, Lewis SG, Hornberger M. (2013) Fronto-striatal grey matter contributions to discrimination learning in Parkinson’s disease. Front Comput Neurosci 7:doi: 10.3389/fncom.2013.00180.
- Patton JH, Stanford JH, Barratt ES. (1995) Factor strucutre of Barratt Impulsiviness Scale. J Clin Psychol 51:768–774.
- Pelloux Y, Dilleen R, Economidou D, Theobald D, Everitt BJ. (2012) Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats. Neuropsychopharmacology 37:2505–2514.
- Seymour B, Daw ND, Roiser JD, Dayan P, Dolan R. (2012) Serotonin selectively modulates reward value in human decision-making. J Neurosci 31:5833–5842.
- Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33;quiz 34–57.
- Sjoerds Z, de Wit S, van den Brink W, Robbins TW, Beekman AT, Penninx BW, Veitman DJ. (2013) Behavioral and neuroimaging evidence for overreliance on habit learning in alcohol-dependant patients. Translational Psychiatry doi: 1038/tp.2013.107.
- Smith KS, Graybiel AM. (2013) A dual operator view of habitual behavior reflecting cortical and striatal dynamics. Neuron 79:361–374.
- Spielberger CD. (1989) State-trait anxiety inventory. 2nd edition Palo Alto, CA: Consulting Psychologist Press.
- Tanaka SC, Balleine BW, O’Doherty JP. (2008) Calculating consequences: brain systems that encode the causal effects of actions. J Neurosci 28:6750–6755.
- Tricomi EM, Balleine BW, O’Doherty JP. (2009) A specific role for posterior dorsolateral striatum in human habit learning. Euro J Neurosci 29:2225–2232.
- van Donkelaar EL, Blokland A, Ferrington L, Kelly PA, Steinbusch HW, Prickaerts J. (2011) Mechanism of acute tryptophan depletion: is it only serotonin? Mol Psychiatry 16:695–713.
- Voon V, Derbyshire K, Rück C, Irvine MA, Worbe Y, Enander J, Schreiber LRN, Gillan CM, Fineberg NA, Sahakian BJ, Robbins TW, Harrison NA, Wood J, Daw ND, Dayan P, Grant JE, Bullmore ET. (2014) Disorders of compulsivity: a common bias towards learning habits. Molecular Psychiatry doi: 10.1038./mp.2014.44.
- Winstanley CA, Dalley JW, Theobald DE, Robbins TW. (2004) Fractionating Impulsivity: contrasting effects of central 5-ht depletion on different measures of impulsive behavior. Neuropsychopharmacology 29:1331–1343.
- Winstanley CA, Theobald DEH, Dalley JW, Robbins TW. (2005) Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders. Neuropsychopharmacology 30:669–682.
- Worbe Y, Savulich G, Voon V, Fernandez-Egea E, Robbins TW. (2014) Serotonin depletion induces “waiting impulsivity” on the human Four Choice Serial Reaction Time Task: cross-species translational significance. Neuropsychopharmacology 39:1519–1526.
Source: PubMed