Chronic Exposure to High Fat Diet Affects the Synaptic Transmission That Regulates the Dopamine Release in the Nucleus Accumbens of Adolescent Male Rats

Author:

Plaza-Briceño Wladimir12,Velásquez Victoria B.12,Silva-Olivares Francisco123,Ceballo Karina12,Céspedes Ricardo12,Jorquera Gonzalo1ORCID,Cruz Gonzalo1ORCID,Martínez-Pinto Jonathan1ORCID,Bonansco Christian1,Sotomayor-Zárate Ramón1ORCID

Affiliation:

1. Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile

2. Programa de Doctorado en Ciencias Mención Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile

3. Instituto de Ciencias Naturales, Facultad de Medicina Veterinaria y Agronomía, Universidad de las Américas, Viña del Mar 2520000, Chile

Abstract

Obesity is a pandemic caused by many factors, including a chronic excess in hypercaloric and high-palatable food intake. In addition, the global prevalence of obesity has increased in all age categories, such as children, adolescents, and adults. However, at the neurobiological level, how neural circuits regulate the hedonic consumption of food intake and how the reward circuit is modified under hypercaloric diet consumption are still being unraveled. We aimed to determine the molecular and functional changes of dopaminergic and glutamatergic modulation of nucleus accumbens (NAcc) in male rats exposed to chronic consumption of a high-fat diet (HFD). Male Sprague-Dawley rats were fed a chow diet or HFD from postnatal day (PND) 21 to 62, increasing obesity markers. In addition, in HFD rats, the frequency but not amplitude of the spontaneous excitatory postsynaptic current is increased in NAcc medium spiny neurons (MSNs). Moreover, only MSNs expressing dopamine (DA) receptor type 2 (D2) increase the amplitude and glutamate release in response to amphetamine, downregulating the indirect pathway. Furthermore, NAcc gene expression of inflammasome components is increased by chronic exposure to HFD. At the neurochemical level, DOPAC content and tonic dopamine (DA) release are reduced in NAcc, while phasic DA release is increased in HFD-fed rats. In conclusion, our model of childhood and adolescent obesity functionally affects the NAcc, a brain nucleus involved in the hedonic control of feeding, which might trigger addictive-like behaviors for obesogenic foods and, through positive feedback, maintain the obese phenotype.

Funder

National Agency of Research and Development

DIUV-CI

FONDECYT

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference73 articles.

1. WHO (2022, December 01). Obesity and Overweight. Available online: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.

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5. Neural Circuit Mechanisms Underlying Emotional Regulation of Homeostatic Feeding;Sweeney;Trends Endocrinol. Metab.,2017

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