Feeding induced by cannabinoids is mediated independently of the melanocortin system.
BACKGROUND
Cannabinoids, the active components of marijuana, stimulate appetite, and cannabinoid receptor-1 (CB1-R) antagonists suppress appetite and promote weight loss. Little is known about how CB1-R antagonists affect the central neurocircuitry, specifically the melanocortin system that regulates energy balance.


RESULTS
Here, we show that peripherally administered CB1-R antagonist (AM251) or agonist equally suppressed or stimulated feeding respectively in A(y) , which lack a functional melanocortin system, and wildtype mice, demonstrating that cannabinoid effects on feeding do not require melanocortin circuitry. CB1-R antagonist or agonist administered into the ventral tegmental area (VTA) equally suppressed or stimulated feeding respectively, in both genotypes. In addition, peripheral and central cannabinoid administration similarly induced c-Fos activation in brain sites suggesting mediation via motivational dopaminergic circuitry. Amperometry-detected increases in evoked dopamine (DA) release by the CB1-R antagonist in nucleus accumbens slices indicates that AM251 modulates DA release from VTA terminals.


CONCLUSIONS
Our results demonstrate that the effects of cannabinoids on energy balance are independent of hypothalamic melanocortin circuitry and is primarily driven by the reward system.
Sinnayah
Puspha
P
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon, United States of America.
Jobst
Erin E
EE
Rathner
Joseph A
JA
Caldera-Siu
Angela D
AD
Tonelli-Lemos
Luciana
L
Eusterbrock
Aaron J
AJ
Enriori
Pablo J
PJ
Pothos
Emmanuel N
EN
Grove
Kevin L
KL
Cowley
Michael A
MA
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D053486:Melanocortins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley
D002186:Cannabinoids; D053486:Melanocortins