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

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.

Dietary intake in children and adolescents with food addiction: A systematic review

“…In addition to sugar, prolonged consumption of high fat concentrations can increase dopamine levels in the nucleus accumbens, amygdala, and prefrontal cortex, resulting in a high sensation of reward-seeking ( Jacques et al, 2019 , Lennerz and Lennerz, 2018 ). An experimental study carried out in young male Sprague–Dawley rats investigated the effect of exposure to a high-fat diet (60 % lipids) for 62 days on dopaminergic modulation in the nucleus accumbens ( Plaza-Briceño et al, 2023 ). In this study, chronic exposure to high lipid concentrations promoted a reduction in dopamine release in the nucleus accumbens, in addition to an increase in body weight and retroperitoneal fat ( Plaza-Briceño et al, 2023 ).…”

“…An experimental study carried out in young male Sprague–Dawley rats investigated the effect of exposure to a high-fat diet (60 % lipids) for 62 days on dopaminergic modulation in the nucleus accumbens ( Plaza-Briceño et al, 2023 ). In this study, chronic exposure to high lipid concentrations promoted a reduction in dopamine release in the nucleus accumbens, in addition to an increase in body weight and retroperitoneal fat ( Plaza-Briceño et al, 2023 ).…”