Dopamine drives binge‐like consumption of a palatable food in experimental Parkinsonism

Abstract

A BS TRACT: Background: Prolonged dopaminergic replacement therapy in PD results in pulsatile dopamine receptors stimulation in both dorsal and ventral striatum causing wearing off, motor fluctuations, and nonmotor side effects such as behavioral addictions. Among impulse control disorders, binge eating can be easily modeled in laboratory animals. Objectives: We hypothesize that manipulation of dopamine levels in a 6-hydroxydopamine-lesioned rats, as a model of PD characterized by a different extent of dopamine denervation between dorsal and ventral striatum, would influence both synaptic plasticity of the nucleus accumbens and binge-like eating behavior. Methods: Food preference, food intake, and weight gain were monitored in sham-operated and unilaterally lesioned rats, subjected to a modified version of Corwin's limited access protocol, modelling binge eating disorder. Electrophysiological properties and long-term potentiation of GABAergic spiny projection neurons of the nucleus accumbens core were studied through ex vivo intracellular and patch-clamp recordings from corticostriatal slices of naïve and L-dopa-treated rats. Results: Sham-operated animals with intact nucleus accumbens core plasticity reliably developed food-addiction-like behavior when exposed to intermittent access to a highly palatable food. In contrast, parkinsonian rats were unresponsive to such restriction regimens, and also plasticity was lost in ventral spiny neurons. Chronic L-dopa reestablished long-term potentiation and compulsive eating, but with a different temporal dynamic that follows that of drug administration. Conclusions: Our data indicate that endogenous and exogenous dopamine drive binge-like consumption of a palatable food in healthy and parkinsonian rats with distinct temporal dynamics, providing new insights into the complexity of L-dopa effects on the mesolimbic dopaminergic system.

A literature review of dopamine in binge eating

“…In pharmacological studies, several drugs including the immediate dopamine precursor L-DOPA [ 75 ], dopamine synthesis inhibitor (alpha-methyl-para-tyrosine [ 53 , 76 , 77 ]), dopamine transporter inhibitors (i.e., methylphenidate [ 47 , 48 , 78 ]; lisdexamfetamine [ 79 , 80 ]; dasotraline [ 81 ]), dopamine receptor agonists (i.e., D1 agonist SKF 81297 [ 56 ]; D2 agonist quinpirole [ 56 ]), and dopamine receptor antagonists (i.e., D1 receptor antagonist SCH 23390 [ 56 , 82 ]; D2 receptor antagonist raclopride [ 82 , 83 ]; D3 receptor antagonist GSK598809 [ 54 ]) have been used to manipulate the dopamine levels and activities.…”

“…An animal study [ 75 ] used male rats that were either dopamine-depleted (n = 30) or dopamine-intact (n = 15), and the dopamine-depleted rats were further randomized into the saline group (n = 15) and L-DOPA group (n = 15). With the intermittent access paradigm, the rats in the dopamine-intact and dopamine-depleted with L-DOPA groups developed binge eating behaviors; however, the rats in the dopamine-depleted with saline were non-responsive to the procedure.…”

Sweets for my sweet: modulation of the limbic system drives salience for sweet foods after deep brain stimulation in Parkinson’s disease

“…Moreover, the firing rate of STN neurons increases due to the delivery of rewards15 16 and STN stimulation elicits impulsive responding to affective stimuli and alters subjective value,17 pointing to a more hedonic than homeostatic-driven eating behaviour. In keeping with these preclinical data, food craving and binge eating were reported in patients with PD after STN DBS with a predominant craving for sweet foods and carbohydrates 18–22. Craving for sweets and chocolate addiction23 24 has also been related to inadequate dopaminergic activity in the reward system 19 25…”

Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

“…In this scenario, experimental models represent important tools for the identification of the pathways involved in the synaptic pathogenesis of psychiatric symptoms in neurological diseases. For instance, evidence derived from preclinical studies suggests that the non-physiological rescue of striatal synaptic plasticity induced by dopamine-replacement therapies may participate in the pathogenesis of ICD during PD [ 196 ]. The loss of the GABAergic tonic inhibition of striatal medium spiny neurons has been proposed as trigger event for obsessive-compulsive-like behavior in an experimental model of HD, suggesting that a dysfunction of cortico-striato-thalamo-cortical transmission is involved in the pathogenesis of psychiatric symptoms in this disease [ 197 ].…”