Aryl hydrocarbon receptor agonists trigger avoidance of novel food in rats.
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of dioxins, but also plays important physiological roles, which are only beginning to unfold. Previous studies have surprisingly unveiled that low doses of the potent AHR agonist TCDD induce a strong and persistent avoidance of novel food items in rats. Here, we further examined the involvement of the AHR in the avoidance response in Sprague-Dawley rats with three established AHR agonists: 6-formylindolo(3,2-b)carbazole (FICZ), β-naphthoflavone (BNF) and benzo[a]pyrene (BaP); with a novel selective AHR modulator (C2); and with an activator of another nuclear receptor, CAR: 2,4,6-tryphenyldioxane-1,3 (TPD). As sensitive indices of AHR or CAR activity, we used Cyp1a1 and Cyp2b1 gene expression, as they are, respectively, the drug-metabolizing enzymes specifically regulated by them. We further attempted to address the roles played by enhanced neophobia and conditioned taste aversion (CTA) in the avoidance behaviour. All AHR agonists triggered practically total avoidance of novel chocolate, but the durations varied. Likewise, acutely subtoxic doses of C2, differing by 25-fold, all elicited a similar outcome. In contrast, TPD did not influence chocolate consumption at all. If rats were initially accustomed to chocolate for 6h after single FICZ or BNF exposure, avoidance was still clearly present two weeks later when chocolate was offered again. Hence, the avoidance response appears to specifically involve the AHR instead of being triggered by induction of intestinal or hepatic nuclear receptor signalling in general. It is also shared by both endogenous and exogenous AHR activators. Moreover, this behavioural change in rats seems to contain elements of both CTA and enhanced neophobia, but further clarification of this is still required.
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Mustialankatu 1, FI-00790 Helsinki, Finland. Electronic address: selma.mahiout@helsinki.fi.
Selma
S
Mahiout
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Mustialankatu 1, FI-00790 Helsinki, Finland.
Raimo
R
Pohjanvirta
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000378:metabolism; D013649:Taste / Q000187:drug effects*; D013997:Time Factors; D019324:beta-Naphthoflavone / Q000494:pharmacology
C111855:6-formylindolo(3,2-b)carbazole; D002227:Carbazoles; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1
AH receptor; Benzo[a]pyrene; FICZ; Novel food avoidance; TPD; β-Naphthoflavone