Dataset Information

High reward expectancy during methylphenidate depresses the dopaminergic response to gain and loss.

ABSTRACT: Dopamine plays an important role in goal-directed behavior, through its modulatory influence on striatal neurons. It is unclear whether tonic dopamine levels, which regulate the vigor of acting, interact with the phasic dopamine response to reward that drives instrumental behavior. In a randomized placebo-controlled study in healthy volunteers, we show that methylphenidate, a drug that increases tonic dopamine levels, systematically reduced striatal phasic BOLD responses to gain and loss in a gambling task as measured with fMRI. It also increased response vigor and reward expectancy-related BOLD signals in the ventral striatum. These findings suggest that striatal tonic dopamine levels constitute an average reward expectation signal that modulates the phasic dopaminergic response to reward. This offers opportunities for treatment of behavioral disorders associated with abnormal reward sensitivity.

SUBMITTER: Evers EA

PROVIDER: S-EPMC5390715 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High reward expectancy during methylphenidate depresses the dopaminergic response to gain and loss.

Evers E A EA Stiers P P Ramaekers J G JG

Social cognitive and affective neuroscience 20170201 2

Dopamine plays an important role in goal-directed behavior, through its modulatory influence on striatal neurons. It is unclear whether tonic dopamine levels, which regulate the vigor of acting, interact with the phasic dopamine response to reward that drives instrumental behavior. In a randomized placebo-controlled study in healthy volunteers, we show that methylphenidate, a drug that increases tonic dopamine levels, systematically reduced striatal phasic BOLD responses to gain and loss in a ga ...[more]

PMID: 27677943

Similar Datasets

Project description:ObjectiveMajor depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals.MethodIn a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride.ResultsDepressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo.ConclusionsAcute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.

Project description:Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is a potential remedial therapy for drug craving and relapse, but the mechanism is poorly understood. We investigated changes in neurotransmitter levels during high frequency stimulation (HFS) of the unilateral NAc on morphine-induced rats. Sixty adult Wistar rats were randomized into five groups: the control group (administration of saline), the morphine-only group (systematic administration of morphine without electrode implantation), the morphine-sham-stimulation group (systematic administration of morphine with electrode implantation but not given stimulation), the morphine-stimulation group (systematic administration of morphine with electrode implantation and stimulation) and the saline-stimulation group (administration of saline with electrode implantation and stimulation). The stimulation electrode was stereotaxically implanted into the core of unilateral NAc and microdialysis probes were unilaterally lowered into the ipsilateral ventral tegmental area (VTA), NAc, and ventral pallidum (VP). Samples from microdialysis probes in the ipsilateral VTA, NAc, and VP were analyzed for glutamate (Glu) and ?-aminobutyric acid (GABA) by high-performance liquid chromatography (HPLC). The levels of Glu were increased in the ipsilateral NAc and VP of morphine-only group versus control group, whereas Glu levels were not significantly changed in the ipsilateral VTA. Furthermore, the levels of GABA decreased significantly in the ipsilateral NAc, VP, and VTA of morphine-only group when compared with control group. The profiles of increased Glu and reduced GABA in morphine-induced rats suggest that the presence of increased excitatory neurotransmission in these brain regions. The concentrations of the Glu significantly decreased while the levels of GABA increased in ipsilateral VTA, NAc, and VP in the morphine-stimulation group compared with the morphine-only group. No significant changes were seen in the morphine-sham stimulation group compared with the morphine-only group. These findings indicated that unilateral NAc stimulation inhibits the morphine-induced rats associated hyperactivation of excitatory neurotransmission in the mesocorticolimbic reward circuit.

Project description:Research on economic decision making has revealed specific biases in gain versus loss domains such that risky choice options are overvalued in gain conditions, implying optimism, but undervalued in loss conditions, implying pessimism. Individual differences in motivational traits and affective states have been shown to predict beliefs and behavior in risky decision making, but it is presently unclear which personal characteristics are most predictive of domain-specific biases. To address this gap in the literature, we investigated the relative influence of positive and negative motivational traits (general sensitivity to rewards and punishments) versus affective states (current levels of positive and negative emotions) on beliefs and choice behavior during a risky economic decision task. We also expanded on previous research by examining how the valence of one's judgment context (positive context tested in Experiment 1, negative context tested in Experiment 2) may determine whether risky choice behavior is more strongly influenced by positive versus negative characteristics. Biases in belief were calculated using an economic decision task that involved estimating the value of risky "stocks" relative to safe "bonds" from experienced outcomes. Experiment 1 used a positive judgment context (likelihood of a "good stock") while Experiment 2 used a negative judgment context (likelihood of a "bad stock"). Consistent with previous findings, we observed a domain-based bias in beliefs about stock values across experiments, such that participants exhibited optimism in gain domain and pessimism in the loss domain. Experiment 1 further revealed that domain-based bias and suboptimal choice behavior was predicted by trait-level reward sensitivity, while positive affective state (PAS) had a more limited influence on belief bias alone. Under the negative judgment context of Experiment 2, there was a similar relationship between reward sensitivity and choice behavior; however, results revealed a slightly stronger influence of negative affective state (NAS). A subsequent cross-study analysis found sensitivity to rewards was most predictive of domain-based biases. These results suggest that motivational traits - particularly those relating to reward sensitivity - are more consistent predictors of domain-based biases and risky choice behavior than affective states, but their predictive power depends the valence of the decision context.

Dataset Information

High reward expectancy during methylphenidate depresses the dopaminergic response to gain and loss.

Publications

High reward expectancy during methylphenidate depresses the dopaminergic response to gain and loss.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets