Mice with Chronically Elevated Dopamine Exhibit Enhanced Motivation, but not Learning, for a Food Reward

Cagniard, Barbara; Balsam, Peter D.; Brunner, Daniela; Zhuang, Xiaoxi

doi:10.1038/sj.npp.1300966

Cited by 235 publications

(199 citation statements)

References 57 publications

(82 reference statements)

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“…On one hand, it has been shown that a DA D3 agonist decreased cocaine self-administration when the workload was high but had no effect when the workload was low (i.e., similar effect to STN DBS) (36). Quite contradictory, it has also been shown that (i) an inactivation of the DA system induced the same kind of effect for food reward (i.e., decreased motivation under high workload and no effect under low workload) (37,38) and (ii) DAT knock-down mice whose characteristic is to have an increased DA transmission showed enhanced motivation for food under high workload (39). To clarify how STN DBS affects DA-related functions, STN and DA systems interactions need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation

Rouaud

Lardeux

Panayotis

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

184

131

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Deep brain stimulation (DBS) is a reversible technique that is currently used for the treatment of Parkinson disease and may be suitable for the treatment of psychiatric disorders. Whether DBS inactivates the target structure is still a matter of debate. Here, from findings obtained in rats, we propose DBS of the subthalamic nucleus (STN) as a possible treatment for cocaine addiction to be further tested in human studies. We show that STN DBS reversibly reduces the motivation to work for an i.v. injection of cocaine, and it increases motivation to work for sucrose pellets. These opposite effects may result from STN DBS effect on the positive affective properties of these rewards. Indeed, we further show that STN DBS reduces the preference for a place previously associated with the rewarding properties of cocaine, and it increases the preference for a place associated with food. Because these findings are consistent with those observed after STN lesions [Baunez C, Dias C, Cador M, Amalric M (2005) Nat Neurosci 8:484-489], they suggest that STN DBS mimics an inactivation of the STN on motivational processes. Furthermore, given that one of the major challenges for cocaine addiction is to find a treatment that reduces the craving for the drug without diminishing the motivation for naturally rewarding activities, our findings validate STN as a good target and DBS as the appropriate technique for a promising therapeutic strategy in the treatment of cocaine addiction.O ver the past decade, there has been an increasing interest in neurosurgical procedures using deep brain stimulation (DBS) to treat neurological and psychiatric disorders, such as Parkinson disease (1, 2) and Huntington disease (3), as well as depression (4) and obsessive compulsive disorders (5).A recent study showing that the effects of subthalamic nucleus (STN) DBS mainly result from a stimulation of the cortico-STN fibers questioned the inactivation of STN by DBS (6). However, there was previously a consensus to consider that action of STN DBS as an inactivation of the cell bodies of the targeted structure with an activation of the passing fibers (7). The mechanisms of DBS remain thus a matter of debate.From the clinical point of view, DBS represents a reversible way to inactivate a particular structure in the brain, a strategy that is preferred to ablative surgery in most cases. The choice of the targeted structure is adapted to the disease.In the case of drug addiction, a devastating disorder whose hallmark feature is an uncontrolled motivation to take the drug while naturally rewarding activities are forsaken, it is crucial to decrease the compulsive motivation for the drug, at the same time preventing decreased motivation for alternative rewarding activities.Because cocaine acts by blocking the dopaminergic transporter, and therefore temporarily increases the amount of dopamine (DA) available in the brain, early treatments for addiction targeted DA system to counteract cocaine effects. However, it is now largely accepted that interfering with the ...

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Section: Discussionmentioning

confidence: 99%

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation

Rouaud

Lardeux

Panayotis

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

184

131

View full text Add to dashboard Cite

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“…More fundamentally, while a number of neuroscientists have shown that the firing of dopamine neurons correlates beautifully to patterns expected from computational models of reward learning, questions have recently emerged about whether the dopamine signals are actually ever needed to cause the learning to occur (Berridge 2007;Cagniard et al 2006a;Palmiter 2007;Panksepp 2005;Redgrave and Gurney 2006). Regarding whether dopamine is needed at all to learn about rewards, several forms of reward learning have recently been shown to proceed normally in the brains of mice that completely lack dopamine signals (due to genetic manipulation that prevents dopamine synthesis by neurons), presumably both phasic and tonic signals (Hnasko et al 2005;Robinson et al 2005).…”

Section: Dopamine-beyond Learning Too?mentioning

confidence: 99%

“…Regarding whether dopamine is needed at all to learn about rewards, several forms of reward learning have recently been shown to proceed normally in the brains of mice that completely lack dopamine signals (due to genetic manipulation that prevents dopamine synthesis by neurons), presumably both phasic and tonic signals (Hnasko et al 2005;Robinson et al 2005). Conversely, elevation of dopamine neurotransmission by a different genetic manipulation may fail to cause or alter teaching signals needed for new reward learning (Cagniard et al 2006a;Cagniard et al 2006b;Niv et al 2007;Tindell et al 2005;Yin et al 2006). Such observations raise room to doubts whether correlations between dopamine signals and learning necessarily imply that the dopamine has a strong causal role in learning.…”

Section: Dopamine-beyond Learning Too?mentioning

confidence: 99%

Affective neuroscience of pleasure: reward in humans and animals

2008

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Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness.

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“…Via the use of c-Fos immunoreactivity, a marker of neuronal activation (Morgan & Curran, 1991;Sheng & Greenberg, 1990), the activity of five brain regions was simultaneously quantified; these were pre-and infralimbic mPFC, NAcc core and shell, and dorsal striatum. Further, it is worth noting that increased levels of ΔFosB, the protein product of another member of the fos family of genes, in the NAcc is associated with increased food motivation (Olausson et al, 2006;Cagniard et al, 2006).By generating neuroanatomical maps of c-Fos immunoreactivity, we were able to discern a fluid and co-varied pattern of activation across the component structures of the mesocorticolimbic DA system that changed as a function of both consumption and the animal's motivational state.…”

Section: Introductionmentioning

confidence: 99%

Dynamic interaction between medial prefrontal cortex and nucleus accumbens as a function of both motivational state and reinforcer magnitude: A c-Fos immunocytochemistry study

2007

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This study examined the effects of simultaneous variations in motivational state (food deprivation) and reinforcer magnitude (food presentation) on c-Fos immunoreactivity in the pre-and infralimbic medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) core and shell, and dorsal striatum. In the first experiment, c-Fos was reliably increased in pre-and infralimbic mPFC of animals 12-and 36-h compared to 0-h deprived. In the second experiment, a small meal (2.5g) selectively increased c-Fos immunoreactivity in both mPFC subdivisions of 36-h deprived animals, as well as in both NAcc subdivisions of 12-h deprived animals. Correlational analyses revealed a changing relationship between mPFC subregions and the NAcc compartments to which they project. In subjects 12-h deprived and allowed a small meal, c-Fos counts in prelimbic mPFC and NAcc core were positively correlated, as were those in infralimbic mPFC and NAcc shell (r = . 83 and .76, respectively). The opposite was true of animals 36-h deprived, with prelimbic mPFC/NAcc core and infralimbic mPFC/ NAcc shell negatively correlated (r = -.85 and -.82, respectively). The third experiment examined the effects of unrestricted feeding (presentation of 20g food) after 0, 12, or 36-h deprivation. No differences between mean c-Fos counts were found, though prelimbic mPFC/NAcc core, and mPFC/ NAcc shell were positively correlated in animals 36-h deprived (r = .76 and .89, respectively). These data suggest that the activity within the mPFC and NAcc, as well as the interaction between the two, change as a complex combinatorial function of motivational state and reinforcer magnitude. Section:

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Mice with Chronically Elevated Dopamine Exhibit Enhanced Motivation, but not Learning, for a Food Reward

Cited by 235 publications

References 57 publications

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation

Affective neuroscience of pleasure: reward in humans and animals

Dynamic interaction between medial prefrontal cortex and nucleus accumbens as a function of both motivational state and reinforcer magnitude: A c-Fos immunocytochemistry study

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