title: 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 ED₅₀ value for the extremely resistant rat line A (LD₅₀) value > 10,000 μg/kg) was 0.36 μg/kg, for the semi-resistant line B (LD₅₀) value 830 μg/kg) 1.07 μg/kg and for the TCDD-sensitive line C (LD₅₀ value 40 μg/kg) 0.34 μg/kg. Interestingly, the ED₅₀ 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.
authors: Department of Environmental Health, National Institute for Health and Welfare (THL), P.O.B. 95, FI-70701 Kuopio, Finland. sanna.lensu@elisanet.fi
authors: Sanna
authors: S
authors: Lensu
authors: Jouni T
authors: JT
authors: Tuomisto
authors: Jouko
authors: J
authors: Tuomisto
authors: Matti
authors: M
authors: Viluksela
authors: Marjo
authors: M
authors: Niittynen
authors: Raimo
authors: R
authors: Pohjanvirta
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1