TY - JOUR
T1 - Dopamine drives binge-like consumption of a palatable food in experimental Parkinsonism
AU - Mineo, Désirée
AU - Cacace, Fabrizio
AU - Mancini, Maria
AU - Vannelli, Anna
AU - Campanelli, Federica
AU - Natale, Giuseppina
AU - Marino, Gioia
AU - Cardinale, Antonella
AU - Calabresi, Paolo
AU - Picconi, Barbara
AU - Ghiglieri, Veronica
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - impulse control disorders
KW - l-dopa
KW - nucleus accumbens
KW - plasticity
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U2 - 10.1002/mds.27683
DO - 10.1002/mds.27683
M3 - Article
AN - SCOPUS:85064614313
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
ER -