Pharmacological modulation of the endocannabinoid signalling alters binge-type eating behaviour in female rats.
OBJECTIVE
Binge eating disorder (BED) is characterized by excessive food intake during short periods of time. Recent evidence suggests that alterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. In this study, we investigated whether pharmacological manipulation of endocannabinoid transmission may be effective in modulating the aberrant eating behaviour present in a validated rat model of BED.


METHODS
Binge-type eating was induced in female rats by providing limited access to an optional source of dietary fat (margarine). Rats were divided into three groups, all with ad libitum access to chow and water: control (C), with no access to margarine; low restriction (LR), with 2 h margarine access 7 days a week; high restriction (HR), with 2 h margarine access 3 days a week.


RESULTS
Compared with the LR group, the HR group consumed more margarine and this was accompanied by an increase in body weight. The cannabinoid CB₁/CB₂ receptor agonist Δ⁹-tetrahydrocannabinol significantly increased margarine intake selectively in LR rats, while the fatty acid amide hydrolase inhibitor URB597 showed no effect. The CB₁ receptor inverse agonist/antagonist rimonabant dose-dependently reduced margarine intake in HR rats. Notably, in HR rats, chronic treatment with a low dose of rimonabant induced a selective long-lasting reduction in margarine intake that did not develop tolerance, and a significant and persistent reduction in body weight.


CONCLUSIONS
Chronic pharmacological blockade of CB₁ receptors reduces binge eating behaviour in female rats and may prove effective in treating BED, with an associated significant reduction in body weight.
Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato (Cagliari), Italy.
M
M
Scherma
L
L
Fattore
V
V
Satta
F
F
Businco
B
B
Pigliacampo
S R
SR
Goldberg
C
C
Dessi
W
W
Fratta
P
P
Fadda
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D056912:Binge-Eating Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000633:toxicity; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000633:toxicity; D054314:Drug Inverse Agonism; D004361:Drug Tolerance; D063388:Endocannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D008383:Margarine / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077285:Rimonabant; D015398:Signal Transduction / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D008383:Margarine; D000077285:Rimonabant