title: Role of systemic endocannabinoid CB-1 receptor antagonism in the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats.
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.
authors.affiliation: Neuropsychology Doctoral Sub-Program, The Graduate Center, City University of New York, United States.
authors.forename: Patricia
authors.initials: P
authors.lastname: Miner
authors.forename: Yana
authors.initials: Y
authors.lastname: Abayev
authors.forename: Ester
authors.initials: E
authors.lastname: Kandova
authors.forename: Meri
authors.initials: M
authors.lastname: Gerges
authors.forename: Esther
authors.initials: E
authors.lastname: Styler
authors.forename: Rachel
authors.initials: R
authors.lastname: Wapniak
authors.forename: Khalid
authors.initials: K
authors.lastname: Touzani
authors.forename: Anthony
authors.initials: A
authors.lastname: Sclafani
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bodnar
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005518:Food Preferences / Q000187:drug effects*; D005632:Fructose / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D012439:Saccharin / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology; D013649:Taste / Q000187:drug effects*
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013549:Sweetening Agents; D005632:Fructose; C103505:AM 251; D012439:Saccharin