Reward and the serotonergic system

doi:10.1016/j.neuroscience.2010.01.036

Neuroscience

Volume 166, Issue 4, 14 April 2010, Pages 1023-1035

https://doi.org/10.1016/j.neuroscience.2010.01.036 Get rights and content

Abstract

Anhedonia, as a failure to experience rewarding stimuli, is a key characteristic of many psychiatric disorders including depression and schizophrenia. Investigations on the neurobiological correlates of reward and hedonia/anhedonia have been a growing subject of research demonstrating several neuromodulators to mediate different aspects of reward processing. Whereas the majority of research on reward mainly focused on the dopamine and opioid systems, a serotonergic mechanism has been neglected. However, recent promising results strengthen the pivotal role of serotonin in reward processing. Evidence includes electrophysical and pharmacological as well as genetic and imaging studies. Primate research using single-unit recording of neurons within the dorsal raphe nucleus argues for a serotonergic mediation of reward value, whereas studies using intracranial self-stimulation point to an important contribution of serotonin in modulating motivational aspects of rewarding brain stimulation. Pharmacological studies using agonists and antagonists of serotonergic receptor subtypes and approaches investigating an increase or decrease of the extracellular level of serotonin offer strong evidence for a serotonergic mediation, ranging from aversion to pleasure. This review provides an argument for serotonin as a fundamental mediator of emotional, motivational and cognitive aspects of reward representation, which makes it possibly as important as dopamine for reward processing.

Section snippets

Cortical and subcortical representations of reward processing

It is important to keep in mind that the term reward comprises multiple components that encompass hedonia, motivation and learning (Salamone et al., 2007, Berridge and Kringelbach, 2008). Major “hedonic hotspots” have been located in the nucleus accumbens shell (NAcc), the ventral pallidum and the parabrachial nucleus of the pons (Berridge and Kringelbach, 2008). Subsets of neurons also encoding motivation have been found within the NAcc and ventral pallidum, and also in the substancia nigra,

Serotonergic projections and reward-related areas

A prerequisite for the hypothesis of a serotonergic account in reward processing is to show that reward related areas are strongly interconnected with serotonergic neurons. The serotonergic system is composed of neurons, whose cell bodies form several nuclei located at the midline of the mesencephalon and medullary brainstem. Among them, two superior nuclei, the dorsal and median raphe nucleus (DRN and MRN), project to a range of limbic and forebrain regions (for reviews, see Lechin et al., 2006

Serotonin transporter and receptor distribution within reward-related areas

Another prerequisite for the above mentioned hypothesis is to show that reward processing areas show distinct densities of 5-HT receptor subtypes, which differentially mediate the effects of serotonergic transmission. Whereas density of the main inhibitory receptor subtype (5-HT_1A) is high in the raphe nuclei, the OFC and ACC, it is low in the VTA, striatum and amygdala (Hall et al., 1997). Density of the main excitatory receptor subtype (5-HT_2A) is high also in OFC and ACC, but low in the

Direct associations between serotonergic neurotransmission and reward processing

Strong support for the hypothesis of this review comes from studies showing either neuronal firing of serotonergic neurons or local release of serotonin to be closely correlated with rewarding experiences or activities. Even more support is received by studies showing rewarding behaviour to be altered due to an experimentally induced alteration of local serotonin release or 5-HT neuron firing.

Effects of changing extracellular serotonin level in the brain

There are numerous studies using rodents, non-human primates and humans that found reward behavior to be altered due to an increase or decrease in serotonin function (see supplementary information). Briefly, studies investigating increased serotonin level using SSRIs in various reward paradigms obtained both reward decreasing (e.g., Hoebel et al., 1989) as well as reward increasing effects (Subhan et al., 2000). Whereas the former effect was mainly interpreted as an inhibitory influence of

Neuroimaging

Although only correlative, neuroimaging studies give the unique opportunity to investigate a potential role of serotonin in reward in human subjects. Especially multimodal neuroimaging studies combining positron emission tomography (PET) and fMRI can demonstrate a potential serotonergic influence on neural activation underlying reward processing.

Genetic evidence

For a comprehensive summary of the genetic account on reward processing, the reader is referred to the supplementary section. There is evidence from rodents (e.g., Bearer et al., 2009), non-human primates (e.g., Watson et al., 2009) and humans (e.g., Frodl et al., 2008, Schmitz et al., 2008) that indicates alterations of both anatomical reward circuits and reward-related behavior associated with gene knockout and polymorphisms of serotonin related genes. Such genetic studies reveal a

Drug reward and the serotonergic system

There is a great corpus of studies showing that serotonin systems have major relevance for reward-related behaviors in the context of drug abuse (see Higgins and Fletcher, 2003, Muller et al., 2007 for review). Although the rewarding effects of drugs are frequently investigated in order to reach a broader understanding of the neurochemical basis of reward in general, in depth analysis of the various aspects of serotonergic function in drug reward would go beyond the scope of this review.

The role of serotonergic antidepressants in reward

Antidepressants that selectively target the serotonergic system (SSRIs) have become the most widely prescribed pharmacotherapy for the treatment of major depression, since they were introduced in the late 1980s. SSRIs have been shown to be effective in alleviating symptoms of general distress in depression in 53%–64% of cases (Hirschfeld, 1999). However, core symptoms such as anhedonia, the loss of interest and decreased motivation are often unaffected by SSRI treatment (Nutt et al., 2007).

Discussion

The main aim of this review is to summarize studies that confirm an essential modulating role of the serotonergic system in reward processing. There is a great amount of anatomical evidence, demonstrating a tight connection between raphe nuclei in the brainstem and several cortical and subcortical areas implicated in reward processing. Although it is important to note that there are several neurotransmitters utilized in the raphe nuclei (Michelsen et al., 2007), their serotonergic projections

Conclusion

There is extensive data supporting an essential modulating role of the serotonergic system in major aspects of reward processing, as well as a change in serotonin transmission accompanied by rewarding activities. We therefore propose that serotonin may be a fundamental mediator of emotional, motivational and cognitive aspects of reward representation, which makes it possibly as important as dopamine for processing reward. However, some limitations have to be taken into account. First, complex

Acknowledgments

With special thanks to Markus Savli, Alexander Holik and Andreas Hahn for their support on the preparation of figures and to Dianne Lorenz for linguistic support. Furthermore, we thank Prof. Dr. Hans Herzog, Institut für Neurowissenschaften und Medizin (INM-4), Forschungszentrum Jülich, for providing the 5-HT_2A maps. Dr. Kasper has received grant/research support from Eli Lilly, Lundbeck, Bristol-Myers Squibb, GlaxoSmithKline, Organon, Sepracor, and Servier; has served as a consultant or on

References (114)

K.C. Ahn et al.
Differential effects of intra-midbrain raphe and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats
Psychopharmacology
(2005)
K.D. Alex et al.
Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission
Pharmacol Ther
(2007)
E. Azmitia
Serotonin
Encyclopedia of life sciences
(2001)
D.J. Balfour
The neuronal pathways mediating the behavioral and addictive properties of nicotine
Handb Exp Pharmacol
(2009)
M.G. Baxter et al.
The amygdala and reward
Nat Rev Neurosci
(2002)
E.L. Bearer et al.
Reward circuitry is perturbed in the absence of the serotonin transporter
Neuroimage
(2009)
K.C. Berridge
Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns
Neurosci Biobehav Rev
(2000)
K.C. Berridge
The debate over dopamine's role in reward: the case for incentive salience
Psychopharmacology
(2007)
K.C. Berridge et al.
Affective neuroscience of pleasure: reward in humans and animals
Psychopharmacology
(2008)
J.R. Bishop et al.
Serotonin 2A -1438 G/A and G-protein Beta3 subunit C825T polymorphisms in patients with depression and SSRI-associated sexual side-effects
Neuropsychopharmacology
(2006)

S. Bose et al.

Effects of 5-hydroxytryptophane on self-stimulation in rats

Psychopharmacologia

(1974)

J. Broadbent et al.

Effects of quipazine and of tryptamine on self-stimulation of median raphe nucleus and of lateral hypothalamus in rats

Pharmacol Biochem Behav

(1985)

P. Cazala

Effects of Lilly 110140 (flouxetine) on self-stimulation behavior in the dorsal and ventral regions of the lateral hypothalamus in the mouse

Psychopharmacology

(1980)

A. Clayton et al.

Burden of phase-specific sexual dysfunction with SSRIs

J Affect Disord

(2006)

R. Cools et al.

Tryptophan depletion disrupts the motivational guidance of goal-directed behavior as a function of trait impulsivity

Neuropsychopharmacology

(2005)

R. Cools et al.

Serotoninergic regulation of emotional and behavioural control processes

Trends Cogn Sci

(2008)

R. Cools et al.

Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction

Neuropsychopharmacology

(2008)

D. Corbett et al.

Intracranial self-stimulation in relation to the ascending noradrenergic fiber systems of the pontine tegmentum and caudal midbrain: a moveable electrode mapping study

Brain Res

(1979)

N.D. Daw et al.

Opponent interactions between serotonin and dopamine

Neural Netw

(2002)

P. Dayan et al.

Serotonin in affective control

Annu Rev Neurosci

(2009)

P. De Deurwaerdere et al.

Role of serotonin(2A) and serotonin(2B/2C) receptor subtypes in the control of accumbal and striatal dopamine release elicited in vivo by dorsal raphe nucleus electrical stimulation

J Neurochem

(1999)

J.F. Deakin

On the neurochemical basis of self-stimulation with midbrain raphe electrode placements

Pharmacol Biochem Behav

(1980)

C.M. Del-Ben et al.

The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study

Neuropsychopharmacology

(2005)

Z.M. Ding et al.

Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats

Psychopharmacology

(2009)

K. Doya

Modulators of decision making

Nat Neurosci

(2008)

E.A. Evers et al.

Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning

Neuropsychopharmacology

(2005)

C. Fahlke et al.

Taste reactivity to ethanol in rats: influence of adrenalectomy or ipsapirone

Alcohol (Fayetteville, NY)

(1994)

S. Fallon et al.

Food reward-induced neurotransmitter changes in cognitive brain regions

Neurochem Res

(2007)

C.F. Ferris et al.

Activation of neural pathways associated with sexual arousal in non-human primates

J Magn Reson Imaging

(2004)

P.J. Fletcher et al.

Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulation

Pharmacol Biochem Behav

(1995)

T. Frodl et al.

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

Mol Psychiatry

(2008)

G. Gobbi et al.

Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study

J Pharmacol Exp Ther

(2001)

F.G. Graeff et al.

Behavioral inhibition induced by electrical stimulation of the median raphe nucleus of the rat

Physiol Behav

(1978)

A. Hahn et al.

Serotonin-1A receptor binding potential in dorsal raphe nuclei predicts orbitofrontal reactivity in healthy subjects

Eur Neuropsychopharmacol

(2009)

H. Hall et al.

Autoradiographic localization of 5-HT(2A) receptors in the human brain using [(3)H]M100907 and [(11)C]M100907

Synapse

(2000)

H. Hall et al.

Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]way-100635

Brain Res

(1997)

J. Hannon et al.

Molecular biology of 5-HT receptors

Behav Brain Res

(2008)

G.C. Harris et al.

A role for lateral hypothalamic orexin neurons in reward seeking

Nature

(2005)

A.A. Harrison et al.

Fluoxetine combined with a serotonin-1A receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats

Neuropsychopharmacology

(2001)

A.A. Harrison et al.

Serotonergic manipulations both potentiate and reduce brain stimulation reward in rats: involvement of serotonin-1A receptors

J Pharmacol Exp Ther

(2001)

A.A. Harrison et al.

RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist

Psychopharmacology

(1999)

D.J. Hayes et al.

Effects of systemic and intra-nucleus accumbens 5-HT(2C) receptor compounds on ventral tegmental area self-stimulation thresholds in rats

Psychopharmacology

(2008)

D.J. Hayes et al.

Effects of systemic 5-HT(1B) receptor compounds on ventral tegmental area intracranial self-stimulation thresholds in rats

Eur J Pharmacol

(2008)

G.A. Higgins et al.

Serotonin and drug reward: focus on 5-HT2C receptors

Eur J Pharmacol

(2003)

O. Hikosaka et al.

New insights on the subcortical representation of reward

Curr Opin Neurobiol

(2008)

R.M. Hirschfeld

Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs

J Clin Psychiatry

(1999)

B.G. Hoebel et al.

Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behaviorTheoretical and clinical implications

Ann N Y Acad Sci

(1989)

A. Izquierdo et al.

Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys

Proc Natl Acad Sci U S A

(2007)

K. Kanno et al.

Ipsilateral and contralateral serotonergic projections from dorsal and median raphe nuclei to the forebrain in rats: immunofluorescence quantitative analysis

Neurosci Res

(2008)

S. Kapur et al.

Serotonin-dopamine interaction and its relevance to schizophrenia

Am J Psychiatry

(1996)

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Behavioural NeuroscienceReviewReward and the serotonergic system

Abstract

Section snippets

Cortical and subcortical representations of reward processing

Serotonergic projections and reward-related areas

Serotonin transporter and receptor distribution within reward-related areas

Direct associations between serotonergic neurotransmission and reward processing

Effects of changing extracellular serotonin level in the brain

Neuroimaging

Genetic evidence

Drug reward and the serotonergic system

The role of serotonergic antidepressants in reward

Discussion

Conclusion

Acknowledgments

Differential effects of intra-midbrain raphe and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats

Psychopharmacology

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Pharmacol Ther

Serotonin

Encyclopedia of life sciences

The neuronal pathways mediating the behavioral and addictive properties of nicotine

Handb Exp Pharmacol

The amygdala and reward

Nat Rev Neurosci

Reward circuitry is perturbed in the absence of the serotonin transporter

Neuroimage

Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns

Neurosci Biobehav Rev

The debate over dopamine's role in reward: the case for incentive salience

Psychopharmacology

Affective neuroscience of pleasure: reward in humans and animals

Psychopharmacology

Serotonin 2A -1438 G/A and G-protein Beta3 subunit C825T polymorphisms in patients with depression and SSRI-associated sexual side-effects

Neuropsychopharmacology

Effects of 5-hydroxytryptophane on self-stimulation in rats

Psychopharmacologia

Effects of quipazine and of tryptamine on self-stimulation of median raphe nucleus and of lateral hypothalamus in rats

Pharmacol Biochem Behav

Effects of Lilly 110140 (flouxetine) on self-stimulation behavior in the dorsal and ventral regions of the lateral hypothalamus in the mouse

Psychopharmacology

Burden of phase-specific sexual dysfunction with SSRIs

J Affect Disord

Tryptophan depletion disrupts the motivational guidance of goal-directed behavior as a function of trait impulsivity

Neuropsychopharmacology

Serotoninergic regulation of emotional and behavioural control processes

Trends Cogn Sci

Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction

Neuropsychopharmacology

Intracranial self-stimulation in relation to the ascending noradrenergic fiber systems of the pontine tegmentum and caudal midbrain: a moveable electrode mapping study

Brain Res

Opponent interactions between serotonin and dopamine

Neural Netw

Serotonin in affective control

Annu Rev Neurosci

Role of serotonin(2A) and serotonin(2B/2C) receptor subtypes in the control of accumbal and striatal dopamine release elicited in vivo by dorsal raphe nucleus electrical stimulation

J Neurochem

On the neurochemical basis of self-stimulation with midbrain raphe electrode placements

Pharmacol Biochem Behav

The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study

Neuropsychopharmacology

Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats

Psychopharmacology

Modulators of decision making

Nat Neurosci

Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning

Neuropsychopharmacology

Taste reactivity to ethanol in rats: influence of adrenalectomy or ipsapirone

Alcohol (Fayetteville, NY)

Food reward-induced neurotransmitter changes in cognitive brain regions

Neurochem Res

Activation of neural pathways associated with sexual arousal in non-human primates

J Magn Reson Imaging

Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulation

Pharmacol Biochem Behav

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

Mol Psychiatry

Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study

J Pharmacol Exp Ther

Behavioral inhibition induced by electrical stimulation of the median raphe nucleus of the rat

Behavioural Neuroscience
Review
Reward and the serotonergic system