Dopamine and eating behavior disorders in Parkinson's disease: A complex recipe

Abstract

Binge or compulsive eating is among the most frequent impulse control disorder occurring following chronic dopamine replacement therapy in Parkinson's disease (PD) patients. 1,2 Food is not only a source of nutrients, but also a potent reward, and the regulation of food intake involves numerous networks, including hypothalamic nuclei, involved in the regulation of energy homeostasis as well as cortico-subcortical circuits involved in reward processing, conditioned responses, and decision making (for review, see a previous work 3 ). All these networks are affected to some extent over the course of PD, with alterations ranging from discrete alpha-synuclein pathology to substantial neurodegeneration.If the role of dopamine in feeding behavior has long been known with the demonstration that lesions of the lateral hypothalamus or substantia nigra pars compacta with 6-OHDA induce adipsia and aphagia in rats, 4 its involvement in binge-eating disorders extends far beyond the simplistic view that dopamine mediates pleasure and reward (for a comprehensive discussion on this topic, see a previous work 5 ). Furthermore, dopaminergic pathways are implicated in different aspects of feeding behavior, with the nigrostriatal system being involved in motor and sensorimotor processes related to food intake, and the mesolimbic system being critical for multiple motivational aspects of feeding behavior such as anticipation, seeking, or wanting. 5 The regulation of feeding behavior in the specific context of PD and dopamine replacement therapy is an intricate matter, and the real impact of the disease process on food intake and eating habits remains difficult to appreciate. Indeed, in addition to the likely altered hedonic values of food and flavors, as well as apathy and anhedonia attributed to the loss of mesencephalic dopaminergic neurons, dopamine is also involved in a number of other processes relevant to feeding behavior, such as sensorimotor integration, planning, anticipation, and movement initiation and execution. Moreover, the variable association of other nonmotor symptoms, such as anosmia, constipation, dysphagia, sialorrhea, cognitive deficits, as well as altered energy expenditure, may also influence eating habits and feeding behavior in PD. 6 The contribution of dopamine replacement therapy to feeding behavior is also far from being a straightforward issue. If drugs elevating extracellular dopamine levels, such a psychostimulants, can exert anorexigenic effects, reduced food intake can also be observed, both with dopamine agonists and antagonists, depending on the doses used or the sites of intracerebral injections, consistent with the involvement of dopamine in many aspects of feeding behavior.Accordingly, investigating the pathophysiological basis of binge-like eating in preclinical models of PD is not a simple task, given that it requires disentangling the contribution of the lesion and subsequent dopamine replacement therapy to the multiple dopamine-dependent aspects of feeding behavior mentioned above.In this issu...

A case–control study investigating food addiction in Parkinson patients

“…Kistner et al 51 proposed that the vast majority of EDs in patients with PD (excluding BED) should be interpreted as subthreshold pathological behaviors in order to compensate for low dopaminergic signaling and called it “hypodopaminergic snacking”. In the present study, no difference was found between PD patients with or without FA in dopamine ligand type and dose, although dopamine is a well-known contributor to addiction through its differentiated roles in reinforcement, motivation and self-regulation 52 – 54 . Interestingly, studies of post-STN stimulation observed that the proportion of patients presenting excessive eating behavior remained high in the follow-up, suggesting that the underlying mechanisms of this specific behavior are complex and need forms of management other than just decreased medication 51 , 55 , 56 .…”