Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis

Mobini, Sirous; Chiang, T.-J.; Al-Ruwaitea, A. S. A.; Ho, M.-Y.; Bradshaw, C. M.; Szabadi, E.

doi:10.1007/s002130000385

Cited by 97 publications

(79 citation statements)

References 32 publications

(40 reference statements)

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“…Mobini et al (2000a, b) found that while global serotonergic depletions altered delay discounting (as one might expect), it did not alter probabilistic discounting, suggesting that serotonin may only influence responses to risk where choice of the less likely options can be reinforced with larger rewards (Mobini et al, 2000a). Long et al (2009) tested for the effects of tryptophan depletion using a tightly controlled paradigm in which macaques were given choices between safe behavioral options and risky behavioral options that carried variable pay-offs (Long et al, 2009).…”

Section: Serotonin and Risky Choicementioning

confidence: 92%

“…In rats, global depletions of serotonin have been shown to increase the value of a hyperbolic discounting parameter for the value of future rewards (Mobini et al, 2000a;Wogar et al, 1993). In humans, (Tanaka et al (2004) have articulated a model in which serotonin is proposed to modulate reinforcement value signals across different time scales within the ventral striatum and the dorsal striatum, respectively.…”

Section: Computational Models Of Serotoninmentioning

confidence: 99%

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The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

Rogers

2010

Neuropsychopharmacol

195

130

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Neurophysiological experiments in primates, alongside neuropsychological and functional magnetic resonance investigations in humans, have significantly enhanced our understanding of the neural architecture of decision making. In this review, I consider the more limited database of experiments that have investigated how dopamine and serotonin activity influences the choices of human adults. These include those experiments that have involved the administration of drugs to healthy controls, experiments that have tested genotypic influences upon dopamine and serotonin function, and, finally, some of those experiments that have examined the effects of drugs on the decision making of clinical samples. Pharmacological experiments in humans are few in number and face considerable methodological challenges in terms of drug specificity, uncertainties about pre-vs post-synaptic modes of action, and interactions with baseline cognitive performance. However, the available data are broadly consistent with current computational models of dopamine function in decision making and highlight the dissociable roles of dopamine receptor systems in the learning about outcomes that underpins value-based decision making. Moreover, genotypic influences on (interacting) prefrontal and striatal dopamine activity are associated with changes in choice behavior that might be relevant to understanding exploratory behaviors and vulnerability to addictive disorders. Manipulations of serotonin in laboratory tests of decision making in human participants have provided less consistent results, but the information gathered to date indicates a role for serotonin in learning about bad decision outcomes, non-normative aspects of risk-seeking behavior, and social choices involving affiliation and notions of fairness. Finally, I suggest that the role played by serotonin in the regulation of cognitive biases, and representation of context in learning, point toward a role in the cortically mediated cognitive appraisal of reinforcers when selecting between actions, potentially accounting for its influence upon the processing salient aversive outcomes and social choice.

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Section: Serotonin and Risky Choicementioning

confidence: 92%

Section: Computational Models Of Serotoninmentioning

confidence: 99%

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

Rogers

2010

Neuropsychopharmacol

195

130

View full text Add to dashboard Cite

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“…Decision-making behavior impinges on cortical/striatal pathways, accounting for processing of incentive values when choosing between two alternatives (Montague and Berns, 2002;Glimcher and Rustichini, 2004;Schultz, 2004). We gave animals a choice between a smaller certain reinforcer and a larger but probabilistic one, a protocol also used to measure impulsivity (Mobini et al, 2000;Evenden, 1999). Economical considerations play, however, a major role in such a protocol.…”

Section: Introductionmentioning

confidence: 99%

Methylphenidate Administration to Adolescent Rats Determines Plastic Changes on Reward-Related Behavior and Striatal Gene Expression

Adriani

Leo

Greco

et al. 2005

Neuropsychopharmacol

107

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Administration of methylphenidate (MPH, Ritalins ) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-related and motivational-choice behaviors. When tested in adulthood in a drug-free state, MPH-pretreated animals showed increased choice flexibility and economical efficiency, as well as a dissociation between dampened place conditioning and more marked locomotor sensitization induced by cocaine, compared to SALpretreated controls. The striatal complex, a core component of the natural reward system, was collected both at the end of the MPH treatment and in adulthood. Genome-wide expression profiling, followed by RT-PCR validation on independent samples, showed that three members of the postsynaptic-density family and five neurotransmitter receptors were upregulated in the adolescent striatum after subchronic MPH administration. Interestingly, only genes for the kainate 2 subunit of ionotropic glutamate receptor (Grik2, also known as KA2) and the 5-hydroxytryptamine (serotonin) receptor 7 (Htr7) (but not GABA A subunits and adrenergic receptor a1b) were still upregulated in adulthood. cAMP responsive element-binding protein and Homer 1a transcripts were modulated only as a long-term effect. In summary, our data indicate short-term changes in neural plasticity, suggested by modulation of expression of key genes, and functional changes in striatal circuits. These modifications might in turn trigger enduring changes responsible for the adult neurobehavioral profile, that is, altered processing of incentive values and a modified flexibility/habit balance.

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“…Central 5-HT manipulations are reported to affect the ability to wait for reinforcement in studies performed with paradigms for either impulsive-choice (e.g. [8,38]) or impulsive-action (e.g. [13,15]).…”

Section: Cognitive Impulsivitymentioning

confidence: 99%

“…[13,15]). For example, lesions of 5-HT pathways [8,15,38] as well as PCPA administration [8,13] resulted in increased impulsivity. Moreover, SERT −/− rats showed increased correct response latency and decreased premature responding in the 5-choice serial reaction time task (5-CSRTT; [24]).…”

Section: Cognitive Impulsivitymentioning

confidence: 99%

Impulsivity and home-cage activity are decreased by lentivirus-mediated silencing of serotonin transporter in the rat hippocampus

Zoratto

Tringle

Bellenchi

et al. 2013

Neuroscience Letters

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h i g h l i g h t s• Lenti-SERT vectors were designed to suppress SERT gene expression in vivo.• We evaluated a rat model of ADHD through hippocampal inoculation of Lenti-SERT.• Lenti-SERT rats exhibited less pronounced peaks of circadian activity than controls.• Lenti-SERT rats displayed a transient decrease in cognitive impulsivity.• Such phenotype is consistent both with 5-HT manipulations and hippocampal lesions.Brain serotonin (5-HT) systems modulate emotional, motivational and cognitive processes. Mutations in the serotonin transporter (SERT) gene have been associated with susceptibility towards the development of several psychiatric disorders, both in humans and animal models. Present approach exploited a bilateral intra-hippocampus stereotaxic inoculation of lentiviruses, for enduring in vivo silencing of SERT. Control rats were bilaterally inoculated with heat-inactivated lentiviruses. These Lenti-SERT vectors were intended to eventually manipulate the neurotransmitter reuptake at synaptic level, thus enhancing tonic 5-HT transmission. We investigated whether such manipulation could induce behavioural alterations relevant to the modelling of ADHD, in particular symptoms of hyperactivity and impulsivity. Wistar rats were monitored for spontaneous home-cage locomotor activity and studied for impulsivity (Intoleranceto-Delay task). Results show that rats inoculated with Lenti-SERT vectors exhibited less pronounced circadian peaks of activity than controls. Moreover, Lenti-SERT compared to control rats exhibited a transient increase in choice for a delayed-larger reward over an immediate-small reward. This suggests that enhanced hippocampal serotonergic transmission produced a profile of restfulness and a decrease in cognitive impulsivity. This phenotype is consistent with available data both on 5-HT manipulations and hippocampal lesions. In conclusion, present findings may possibly disclose novel avenues towards the development of innovative therapeutical approaches for behavioural symptoms relevant to ADHD.

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Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis

Abstract: According to the multiplicative hyperbolic model, parallel displacement of the linear indifference function uniquely specifies a change in time discounting. Thus these results indicate that central 5-HT depletion results in an increase in the rate of time discounting for food reinforcers.

Cited by 97 publications

References 32 publications

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

Methylphenidate Administration to Adolescent Rats Determines Plastic Changes on Reward-Related Behavior and Striatal Gene Expression

Impulsivity and home-cage activity are decreased by lentivirus-mediated silencing of serotonin transporter in the rat hippocampus

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