Immediate and highly sensitive aversion response to a novel food item linked to AH receptor stimulation

Abstract

Aversion to novel food items was studied in male rats and mice after 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) exposure using chocolate consumption as an indicator. The correlation of this phenomenon with susceptibility to acute toxicity and CYP1A1 induction was examined by determining the dose–response of chocolate aversion in differently dioxin-sensitive rat lines after TCDD (0.01–10 μg/kg). Furthermore, the dependence of this behavioral alteration on the AH receptor (AHR) was studied employing AHR-deficient and wild-type mice. We offered chocolate for both species as a novel food item immediately after the exposure, and it was available with standard rodent chow for 3 days. The ED 50 value for the extremely resistant rat line A (LD 50 value > 10,000 μg/kg) was 0.36 μg/kg, for the semi-resistant line B (LD 50 value 830 μg/kg) 1.07 μg/kg and for the TCDD-sensitive line C (LD 50 value 40 μg/kg) 0.34 μg/kg. Interestingly, the ED 50 values for chocolate aversion were very similar to those for CYP1A1 induction in these rat lines. Findings on AHR-deficient and wild-type mice implied the involvement of the AHR in this intriguing response, which may thus represent a mechanism to restrict exposure to potentially toxic dietary substances causing hepatic induction of drug-metabolizing enzymes.