Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure

Abstract

Obesity-related pathologies and anorexia nervosa are increasingly considered as opposite ends of eating disorders (ED) spectrum. Accordingly, accumulating evidence points to opposite dysregulations of common brain systems in these pathologies, the Nucleus Accumbens (NAc) in particular. However, to which extent alterations in NAc activity are sufficient to elicit ED-like behavioral dimensions remains to be established. Using acute, bidirectional, chemogenetic modulation of each NAc medium spiny neuron (MSN) subpopulation, we found that D1-MSNs and D2-MSNs oppositely regulate the balance between food intake and exercise-induced energy expenditure. As opposed to the limited effect of repeated chemogenetic manipulations of each MSN subpopulation, the concomitant manipulation of both MSN subpopulation had sustained effects. Repeated activation of D1-MSNs combined with repeated inhibition of D2-MSNs biased behavior toward activity-related energy expenditure leading to weight/fat loss, whilst the opposite manipulations favored energy intake and hence weight/fat gain. These results suggest that dysregulations of NAc dopaminoceptive MSN network might be at the core of EDs.

Reduced GABA transmission onto ventral tegmental area dopamine neurons underlies vulnerability for hyperactivity in a mouse model of Anorexia Nervosa

“…The results obtained in this study are in accordance with the hypothesized relationship between the hyperdopaminergic function and the regulation of energy expenditure [51]: low dopamine function leads to restrictive behaviors (conserve energy/exploit environment) whereas higher dopamine function drives expansive behaviors (expend energy/explore environment). This is supported by a growing number of studies manipulating dopamine transmission in ABA-exposed animals and showing that increased dopamine transmission leads to higher vulnerability to body weight loss [22, 26, 29, 52]. Additionally, running wheel activity has been shown to increase striatal DA release and induce a hyperdopaminergic state [53, 54].…”

“…Animal studies support the link between the DA reward system and the regulation of energy homeostasis. DA transmission in the ventral tegmental area (VTA) is involved in energy homeostasis by regulating both exercise and feeding behaviors [17][18][19][20][21][22]. The activity-based anorexia (ABA) model is typically used to better understand the neurobiology of AN and evaluate potential treatment targets (for review see [23,24]).…”