A high-refined carbohydrate diet facilitates compulsive-like behavior in mice through the nitric oxide pathway

• Published in: Nitric oxide 2018-11, Vol.80, p.61-69
• Main Authors: Gomes, Júlia Ariana Souza, Oliveira, Marina C., Gobira, Pedro Henrique, Silva, Grazielle C., Marçal, Anna Paula, Gomes, Giovanni Freitas, Ferrari, Carolina Zaniboni, Lemos, Virginia Soares, Oliveira, Antonio Carlos Pinheiro de, Vieira, Luciene Bruno, Ferreira, Adaliene V.M., Aguiar, Daniele C.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Cocaine - pharmacology; Compulsive Behavior - etiology; Compulsive-like behavior; Conditioning (Psychology) - drug effects; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Diet; Diet, Carbohydrate Loading - adverse effects; Dietary Carbohydrates - adverse effects; High-carbohydrate; Interleukin-6 - metabolism; Male; Marble-burying test; Mice, Inbred BALB C; Neuroinflammation; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - metabolism; Potassium - metabolism
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2018.08.008

Obesity is characterized by abnormal adipose tissue expansion and is associated with chronic inflammation. Obesity itself may induce several comorbidities, including psychiatric disorders. It has been previously demonstrated that proinflammatory cytokines are able to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release, which both have a role in compulsive related behaviors. To evaluate whether acute or chronic consumption of a high-refined carbohydrate-containing (HC) diet will modify burying-behavior in the Marble Burying Test (MBT) through augmentation of NO signaling in the striatum, a brain region related to the reward system. Further, we also verified the effects of chronic consumption of a HC diet on the reinforcing effects induced by cocaine in the Conditioned Place Preference (CPP) test. Male BALB/c mice received a standard diet (control diet) or a HC diet for 3 days or 12 weeks. An increase in burying behavior occurred in the MBT after chronic consumption of a HC diet that was associated with an increase of nitrite levels in the striatum. The pre-treatment with Aminoguanidine (50 mg/kg), a preferential inhibitor of iNOS, prevented such alterations. Additionally, a chronic HC diet also induced a higher expression of iNOS in this region and higher glutamate release from striatal synaptosomes. Neither statistical differences were observed in the expression levels of the neuronal isoform of NOS nor in microglia number and activation. Finally, the reinforcing effects induced by cocaine (15 mg/kg, i.p.) during the expression of the conditioned response in the CPP test were not different between the chronically HC diet fed mice and the control group. However, HC diet-feeding mice presented impairment of cocaine-preference extinction. Altogether, our results suggest that the chronic consumption of a HC diet induces compulsive-like behavior through a mechanism possibly associated with NO activation in the striatum. •Chronic consumption of a high-sugar diet induced compulsive-like behavior.•A high-sugar diet increased NO levels in the striatum after a chronic period.•Inhibition of iNOS prevented behavior impairment promoted by a high-sugar diet.•Conditioned reward memory was persistent after high-sugar consumption.