Prefrontal Cortical Control of Activity in Nucleus Accumbens Core Is Weakened by High-Fat Diet and Prevented by Co-Treatment with N-Acetylcysteine: Implications for the Development of Obesity

Abstract

A loss of neuroplastic control on nucleus accumbens (NAc) neuronal activity exerted by the medial prefrontal cortex (mPFC) through long-term depression (LTD) is involved in triggering drug-seeking behavior and relapse on several substances of abuse due to impaired glutamate homeostasis in tripartite synapses of the nucleus accumbens (NAc) core. To test whether this maladaptive neuroplastic mechanism underlies the addiction-like behavior induced in young mice by a high-fat diet (HFD), we utilized 28-days-old male mice fed HFD ad-libitum over 2 weeks, followed by 5 days of HFD abstinence. Control groups were fed a regular diet. HFD fed mice showed increased ΔFosB levels in the NAc core region, whereas LTD triggered from the mPFC became suppressed. Interestingly, LTD suppression was prevented by an i.p. injection of 100 mg/kg N-acetylcysteine 2.5 h before inducing LTD from the mPFC. In addition, excessive weight gain due to HFD feeding was diminished by adding 2mg/mL N-acetylcysteine in drinking water. Those results show a loss of neuroplastic mPFC control over NAc core activity induced by HFD consumption in young subjects. In conclusion, ad libitum consumption of HFD can lead to neuroplastic changes an addiction-like behavior that can be prevented by N-acetylcysteine, helping to decrease the rate of excessive weight gain.

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties

“…High fat and sugar accumulation has been associated with opioid and dopamine receptor activation in the nucleus accumbens, the brain area controlling the development of cravings [ 121 , 133 ]. Furthermore, fructose increases blood flow to the brain region responsible for motivation and reward, failing to reduce satiety and contributing to obesity in NAFLD [ 121 ].…”

“…Furthermore, fructose increases blood flow to the brain region responsible for motivation and reward, failing to reduce satiety and contributing to obesity in NAFLD [ 121 ]. This activation of reward centers in response to certain macronutrients is coupled to the systemic reduction of glucagon-like peptide 1 (GLP-1) and the increase in ghrelin, both gut-derived hormones that promote satiety and stimulate hunger [ 133 ]. As a result of these changes, circulating triglyceride levels increase, which has implications for pathogenesis [ 134 ].…”