Interactions between endocannabinoids and stress-induced decreased sensitivity to natural reward.
Since endocannabinoids modulate reward processing and the stress response, we tested the hypothesis that endocannabinoids regulate stress-induced decreased sensitivity to natural reward. Restraint was used to produce stress-induced reductions in sucrose consumption and preference in male mice. Central cannabinoid receptor (CB(1)) signaling was modulated pharmacologically prior to the application of stress. The preference for sucrose over water was significantly decreased in mice exposed to restraint. Treatment of mice with a cannabinoid receptor agonist (CP55940) or fatty acid amide hydrolase inhibitor (URB597) attenuated, while the CB(1) receptor antagonist/inverse agonist, rimonabant (SR141716), enhanced, stress-induced decreases in sucrose preference. These data are consistent with a tonically active, stress-inhibitory role for the CB(1) receptor. Mice treated with 10 daily episodes of restraint showed reduced sucrose preference that was unaffected by CP55940 and URB597. However, rimonabant produced a greater reduction in sucrose preference on day 10 compared to day 1. These data suggest that on day 10, endocannabinoid signaling is maximally activated and essential for reward sensitivity. The findings of the present study indicate that the CB(1)/endocannabinoid signaling system is an important allostatic mediator that both modulates the responses of mice to stress and is itself modulated by stress.
Rademacher
David J
DJ
Medical College of Wisconsin, Department of Pharmacology and Toxicology, 8701 Watertown Plank Road, Milwaukee, WI 53226 USA. david.rademacher@rosalindfranklin.edu
Hillard
Cecilia J
CJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001549:Benzamides / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002219:Carbamates / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D003511:Cyclohexanols; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004347:Drug Interactions; D063388:Endocannabinoids; D005508:Food Deprivation; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012149:Restraint, Physical / Q000009:adverse effects; D012201:Reward; D000077285:Rimonabant; D013315:Stress, Psychological / Q000503:physiopathology*; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors; D014868:Water Deprivation / Q000502:physiology
D001549:Benzamides; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D003510:Cyclohexanes; D003511:Cyclohexanols; D063388:Endocannabinoids; D010636:Phenols; D010880:Piperidines; D011720:Pyrazoles; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D013395:Sucrose; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant