The mycotoxin deoxynivalenol activates GABAergic neurons in the reward system and inhibits feeding and maternal behaviours

• Published in: Archives of toxicology 2020-09, Vol.94 (9), p.3297-3313
• Main Authors: Csikós, Vivien, Varró, Petra, Bódi, Veronika, Oláh, Szilvia, Világi, Ildikó, Dobolyi, Arpád
• Format: Article
• Language: English
• Subjects: Activation; Animal behavior; Animal health; Biologics; Biomedical and Life Sciences; Biomedicine; c-Fos protein; Circuits; Deoxynivalenol; Environmental Health; Fungi; Fusarium graminearum; Immunohistochemistry; Injection; Labeling; Maternal behavior; Motivation; Mycotoxins; Neurons; Nucleus accumbens; Nursing; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Place preference conditioning; Pollutants; Prefrontal cortex; Reinforcement; Taste aversion; Ventral tegmentum; γ-Aminobutyric acid
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-020-02791-6

Deoxynivalenol (DON) or vomitoxin, is a trichothecene mycotoxin produced mainly by Fusarium graminearum and culmorum. Mycotoxins or secondary metabolic products of mold fungi are micro-pollutants, which may affect human and animal health. The neuronal and behavioural actions of DON were analysed in the present study. To address, which neurons can be affected by DON, the neuronal activation pattern following intraperitoneal injection of DON (1 mg/kg) was investigated in adult male rats and the results were confirmed in mice, too. DON-induced neuronal activation was assessed by c-Fos immunohistochemistry. DON injection resulted in profound c-Fos activation in only the elements of the reward system, such as the accumbens nucleus, the medial prefrontal cortex, and the ventral tegmental area. Further double labelling studies suggested that GABAergic neurons were activated by DON treatment. To study the behavioural relevance of this activation, we examined the effect of DON on feed intake as an example of reward-driven behaviours. Following DON injection, feed consumption was markedly reduced but returned to normal the following day suggesting an inhibitory action of DON on feed intake without forming taste-aversion. To further test how general the effect of DON on goal-directed behaviours is, its actions on maternal behaviour was also examined. Pup retrieval latencies were markedly increased by DON administration, and DON-treated mother rats spent less time with nursing suggesting reduced maternal motivation. In a supplementary control experiment, DON did not induce conditioned place preference arguing against its addictive or aversive actions. The results imply that acute uptake of the mycotoxin DON can influence the reward circuit of the brain and exert inhibitory actions on goal-directed, reward-driven behaviours. In addition, the results also suggest that DON exposure of mothers may have specific implications.