Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c-Fos expression in the hypothalamus.
OBJECTIVE
Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.


METHODS
Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections.


RESULTS
Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB(1) antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT.


CONCLUSIONS
These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.
Soria-Gómez
E
E
Grupo de Neurociencias, Depto. de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico DF 04510, Mexico.
Matias
I
I
Rueda-Orozco
P E
PE
Cisneros
M
M
Petrosino
S
S
Navarro
L
L
Di Marzo
V
V
Prospéro-García
O
O
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001593:Benzyl Compounds / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism* / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D001593:Benzyl Compounds; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D012701:Serotonin; D000099252:Fatty Acid Amide Hydrolases; C474344:OMDM-1 cpd; C114007:arachidonoylserotonin; C103505:AM 251; C094503:glyceryl 2-arachidonate; C078814:anandamide