Obesity is a leading public health problem worldwide. Multiple lines of evidence associate deficits in the brain reward circuit with obesity.Whether alterations in brain reward sensitivity precede or are a consequence of obesity is unknown. This study aimed to investigate both innate and obesity-induced differences in the sensitivity to the effects of an indirect dopaminergic agonist.Rats genetically prone to diet-induced obesity (DIO) and their counterpart diet-resistant (DR) were fed a chow diet, and their response to d-amphetamine on intracranial self-stimulation and food intake were assessed. The same variables were then evaluated after exposing the rats to a high-fat diet, after DIO rats selectively developed obesity. Finally, gene expression levels of dopamine receptors 1 and 2 as well as tyrosine hydroxylase were measured in reward-related brain regions.In a pre-obesity state, DIO rats showed innate decreased sensitivity to the reward-enhancing and anorectic effects of d-amphetamine, as compared to DR rats. In a diet-induced obese state, the insensitivity to the potentiating effects of d-amphetamine on intracranial self-stimulation (ICSS) threshold persisted and became more marked in DIO rats, while the anorectic effects were comparable between genotypes. Finally, innate and obesity-induced differences in the gene expression of dopamine receptors were observed.Our results demonstrate that brain reward deficits antedate the development of obesity and worsen after obesity is fully developed, suggesting that these alterations represent vulnerability factors for its development. Moreover, our data suggests that the reward-enhancing and anorectic effects of d-amphetamine are dissociable in the context of obesity.

Diet-induced obesity and diet-resistant rats: differences in the rewarding and anorectic effects of d-amphetamine / Valenza, Marta; Steardo, Luca; Cottone, Pietro; Sabino, Valentina. - In: PSYCHOPHARMACOLOGY. - ISSN 0033-3158. - 232:17(2015), pp. 3215-3226. [10.1007/s00213-015-3981-3]

Diet-induced obesity and diet-resistant rats: differences in the rewarding and anorectic effects of d-amphetamine

Valenza, Marta;Steardo, Luca;Cottone, Pietro;
2015

Abstract

Obesity is a leading public health problem worldwide. Multiple lines of evidence associate deficits in the brain reward circuit with obesity.Whether alterations in brain reward sensitivity precede or are a consequence of obesity is unknown. This study aimed to investigate both innate and obesity-induced differences in the sensitivity to the effects of an indirect dopaminergic agonist.Rats genetically prone to diet-induced obesity (DIO) and their counterpart diet-resistant (DR) were fed a chow diet, and their response to d-amphetamine on intracranial self-stimulation and food intake were assessed. The same variables were then evaluated after exposing the rats to a high-fat diet, after DIO rats selectively developed obesity. Finally, gene expression levels of dopamine receptors 1 and 2 as well as tyrosine hydroxylase were measured in reward-related brain regions.In a pre-obesity state, DIO rats showed innate decreased sensitivity to the reward-enhancing and anorectic effects of d-amphetamine, as compared to DR rats. In a diet-induced obese state, the insensitivity to the potentiating effects of d-amphetamine on intracranial self-stimulation (ICSS) threshold persisted and became more marked in DIO rats, while the anorectic effects were comparable between genotypes. Finally, innate and obesity-induced differences in the gene expression of dopamine receptors were observed.Our results demonstrate that brain reward deficits antedate the development of obesity and worsen after obesity is fully developed, suggesting that these alterations represent vulnerability factors for its development. Moreover, our data suggests that the reward-enhancing and anorectic effects of d-amphetamine are dissociable in the context of obesity.
2015
Dopamine receptors; Dorsal striatum; Food intake OR feeding; High-fat OR high fat; Intracranial self-stimulation OR ICSS; Obesity OR obese; Nucleus accumbens; Reward; Ventral tegmental area OR VTA
01 Pubblicazione su rivista::01a Articolo in rivista
Diet-induced obesity and diet-resistant rats: differences in the rewarding and anorectic effects of d-amphetamine / Valenza, Marta; Steardo, Luca; Cottone, Pietro; Sabino, Valentina. - In: PSYCHOPHARMACOLOGY. - ISSN 0033-3158. - 232:17(2015), pp. 3215-3226. [10.1007/s00213-015-3981-3]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1702932
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