Putting desire on a budget: dopamine and energy expenditure, reconciling reward and resources

Abstract

Accumulating evidence indicates integration of dopamine function with metabolic signals, highlighting a potential role for dopamine in energy balance, frequently construed as modulating reward in response to homeostatic state. Though its precise role remains controversial, the reward perspective of dopamine has dominated investigation of motivational disorders, including obesity. In the hypothesis outlined here, we suggest instead that the primary role of dopamine in behavior is to modulate activity to adapt behavioral energy expenditure to the prevailing environmental energy conditions, with the role of dopamine in reward and motivated behaviors derived from its primary role in energy balance. Dopamine has long been known to modulate activity, exemplified by psychostimulants that act via dopamine. More recently, there has been nascent investigation into the role of dopamine in modulating voluntary activity, with some investigators suggesting that dopamine may serve as a final common pathway that couples energy sensing to regulated voluntary energy expenditure. We suggest that interposed between input from both the internal and external world, dopamine modulates behavioral energy expenditure along two axes: a conserve-expend axis that regulates generalized activity and an explore-exploit axes that regulates the degree to which reward value biases the distribution of activity. In this view, increased dopamine does not promote consumption of tasty food. Instead increased dopamine promotes energy expenditure and exploration while decreased dopamine favors energy conservation and exploitation. This hypothesis provides a mechanistic interpretation to an apparent paradox: the well-established role of dopamine in food seeking and the findings that low dopaminergic functions are associated with obesity. Our hypothesis provides an alternative perspective on the role of dopamine in obesity and reinterprets the "reward deficiency hypothesis" as a perceived energy deficit. We propose that dopamine, by facilitating energy expenditure, should be protective against obesity. We suggest the apparent failure of this protective mechanism in Western societies with high prevalence of obesity arises as a consequence of sedentary lifestyles that thwart energy expenditure.

Keywords: basal ganglia; cost sensitivity; dopamine; effort; energy management; explore-exploit; incentive-salience; reward.

Figure 1

Two axes conceptual framework for regulation of behavioral energy expenditure by dopamine. The horizontal axes represents dopamine's role in regulating generalized activity levels along a continuum from low activity (conserve) to high activity (expend). The vertical axes represent the role of dopamine in regulating the balance between exploration and exploitation by modulating the degree to which reward information biases the distribution of behavioral activity. “Dopamine function” is construed broadly here and may include not only extracellular concentrations of dopamine in target regions, activity of dopamine neurons (i.e., rate of tonic activity, prevalence of bursting) but also parameters such as relative expression of different receptors (e.g., D1 and D2), expression and activity of the doapmine transporter (DAT) as well as properties of vesicular release, including size of readily releaseable pool and vesicle size. As a general conceptual principle, we associate reduced dopamine function with conservation and exploitation (lower left quadrant) and increased dopamine function with expenditure and exploration (upper right quadrant), as reflected by the larger arrow. However, alterations of different aspects of the dopamine system (for example, shifting the relative expression of D1 and D2 receptors) may shift this relationship, generating behavior described by the other quadrants, such as high expenditure coupled with a greater exploitation of reward information (lower right quadrant).

Figure 2

Role of direct and indirect pathway modulation of corticostriatal throughput in regulating the energy expenditure. The striatum modulates cortical processing via corticostriatal-thalamocortical loops through the basal gangia through two pathways, the direct, nigrostriatal (“GO”) and the indirect, striatopallidal (“NOGO”), expressing predominantly D1 and D2 dopamine receptors, respectively. Acting on D1 in the GO pathway (red toned boxes), dopamine disinhibits corticostriatal throughput facilitating activity while dopamine activation of D2 inhibits the NOGO pathway (blue toned boxes), also facilitating activity by dampening the inhibitory influence of the indirect. Conversely, decreases in dopamine diminish D1 mediated disinhibition of the GO pathway and D2 mediated inhibition of the NOGO pathway, both serving to restrict corticostriatal throughput. These dopamine effects are represented by green arrows for the GO pathways, indicating facilitation of corticostriatal throughput and red stop arrows for the NOGO pathway indicating inhibition of corticostriatal throughput. The consequences of increased and decreased dopamine on the expenditure and distribution of energy is summarized below with the two axes (conserve-expend and explore-exploit) collapses on a single scale of restrictive deployment of energy (constrained expenditure focused on exploiting reward information) versus expansive energy expenditure (high expenditure distributed liberally to behavioral activities, i.e., exploration), where restrictive energy use is represented by blue and expansive energy use by red.