Role of systemic endocannabinoid CB-1 receptor antagonism in the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats.

Full Abstract

Rats learn to prefer a flavor mixed into a fructose-saccharin solution over a different flavor mixed into a saccharin-only solution which is considered to be a form of flavor-flavor conditioning. Fructose-conditioned flavor preferences are impaired by systemic dopamine D1 and to a lesser degree, D2 receptor antagonism as well as by NMDA, but not opioid, receptor antagonism. Given the emerging role of the endocannabinoid system in mediating hedonically-driven food intake, the present study examined whether systemic administration of the inverse CB-1 receptor agonist, AM-251 would alter fructose-conditioned flavor preferences. In Experiment 1, food-restricted rats were trained over 10 sessions (30 min/day) to drink a fructose-saccharin solution mixed with one flavor (CS+/Fs) and a less-preferred saccharin-only solution mixed with another flavor (CS-/s). Subsequent two-bottle tests with the two flavors in saccharin (CS+/s, CS-/s) occurred 15 min following counterbalanced pairs of AM-251 doses of 0, 0.1, 1 or 3 mg/kg. Preference for CS+/s over CS-/s following vehicle treatment (74%) was significantly reduced by the 0.1 (67%) and 1 (65%) AM-251 doses, whereas CS+/s, but not CS-/s intake was significantly reduced by the 1 and 3 mg/kg AM-251 doses. In Experiment 2, rats received systemic injections of AM-251 (1 mg/kg) or vehicle prior to the 10 CS+/Fs and CS-/s training sessions. In subsequent two-bottle tests (drug-free) the AM-251 and control groups displayed similar preferences for the CS+ flavor (66% vs. 69%). Experiment 3 demonstrated that AM-251 significantly decreased chow intake (24 h), and 1-h intakes of fructose-saccharin and saccharin-only solutions in ad libitum-fed rats. These data indicate that functional CB-1 receptor antagonism significantly reduces the expression, but not the acquisition of fructose-conditioned flavor-flavor preferences. The endogenous endocannabinoid system is therefore implicated in the maintenance of this form of learned flavor preferences.

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Author information

Author/s: Miner, Patricia (P); Abayev, Yana (Y); Kandova, Ester (E); Gerges, Meri (M); Styler, Esther (E); Wapniak, Rachel (R); Touzani, Khalid (K); Sclafani, Anthony (A); Bodnar, Richard J (RJ);

Affiliation: Neuropsychology Doctoral Sub-Program, The Graduate Center, City University of New York, United States.

Grants: DK071761 (Agency:United States NIDDK)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav), published in United States. (Language: eng)

Reference: 2008-Sep; vol 90 (issue 3) : pp 318-24

Dates: Created 2008/06/09; Completed 2008/08/25;

PMID: 18407342, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Conditioning, Operant - drug effects
Dose-Response Relationship, Drug
Food Preferences - drug effects
Fructose - pharmacology
Male
Piperidines - pharmacology

Pyrazoles - pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 - antagonists & inhibitors
Saccharin - pharmacology
Sweetening Agents - pharmacology
Taste - drug effects

Associated Chemicals: AM 251 (0) ; Piperidines (0) ; Pyrazoles (0) ; Receptor, Cannabinoid, CB1 (0) ; Sweetening Agents (0) ; Fructose (30237-26-4) ; Saccharin (81-07-2)

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