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Aryl hydrocarbon receptor agonists trigger avoidance of novel food in rats.
- Source :
-
Physiology & behavior [Physiol Behav] 2016 Dec 01; Vol. 167, pp. 49-59. Date of Electronic Publication: 2016 Sep 01. - Publication Year :
- 2016
-
Abstract
- 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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Analysis of Variance
Animals
Benzo(a)pyrene metabolism
Benzo(a)pyrene pharmacology
Carbazoles pharmacology
Cytochrome P-450 CYP1A1 genetics
Cytochrome P-450 CYP1A1 metabolism
Cytochrome P-450 CYP2B1 genetics
Cytochrome P-450 CYP2B1 metabolism
Dose-Response Relationship, Drug
Eating drug effects
Male
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Receptors, Aryl Hydrocarbon metabolism
Time Factors
beta-Naphthoflavone pharmacology
Avoidance Learning drug effects
Feeding Behavior drug effects
Food Preferences drug effects
Receptors, Aryl Hydrocarbon agonists
Taste drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-507X
- Volume :
- 167
- Database :
- MEDLINE
- Journal :
- Physiology & behavior
- Publication Type :
- Academic Journal
- Accession number :
- 27594096
- Full Text :
- https://doi.org/10.1016/j.physbeh.2016.08.033