Influence of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist (WIN 55,212-2) and inverse agonist (AM 251) on the regulation of food intake and hypothalamic serotonin levels.
The effect of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist WIN 55,212-2 or inverse agonist AM 251 on food intake and extracellular levels of serotonin and acetic acid 5-hydroxy-indol from presatiated rats was studied. Compared to the vehicle-injected control, the intracerebroventricular administration of WIN 55,212-2 was associated with a significant increase in food intake, whereas the administration of AM 251 caused a significant reduction in this respect. These results were accompanied by considerable reductions or increases in serotonin and acetic acid 5-hydroxy-indol levels compared to the vehicle-injected control and the baseline values for the different experimental groups studied. Intraperitoneal administration of WIN 55,212-2 at doses of 1 and 2 mg/kg promoted hyperphagia up to 6 h after injection, whereas administration of a higher dose (5 mg/kg) significantly inhibited food intake and motor behaviour in partially satiated rats. Administration of any of the AM 251 doses studied (0.5, 1, 2, 5 mg/kg) led to a significant decrease in the amount of food ingested from 2 h after the injection, compared to the vehicle-injected control group, with the most striking effect being observed when the 5 mg/kg dose was injected.
Merroun
Ikram
I
Department of Physiology, School of Pharmacy, University of Granada, Campus University of Granada s/n, Granada, Spain.
Errami
Mohammed
M
Hoddah
Hanaa
H
Urbano
Gloria
G
Porres
Jesús M
JM
Aranda
Pilar
P
Llopis
Juan
J
López-Jurado
María
M
D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D002552:Cerebral Ventricles; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D045604:Extracellular Fluid / Q000737:chemistry; D015870:Gene Expression; D016762:Genes, fos; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D012701:Serotonin; C103505:AM 251; D006897:Hydroxyindoleacetic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone