Central cannabinoid signaling mediating food intake: a pharmacological-challenge magnetic resonance imaging and functional histology study in rat.
Endocannabinoids have a variety of effects by acting through cannabinoid 1 (CB1) receptors located throughout the brain. However, since CB1 receptors are located presynaptically, and because the strength of downstream coupling varies with brain region, expression studies alone do not provide a firm basis for interpreting sites of action. Likewise, to date most functional studies have used high doses of drugs, which can bias results toward non-relevant adverse effects, and which mask more behaviourally-relevant actions. Here we use a low, orexigenic dose of the full CB1 agonist, CP55940, to map responsive brain regions using the complementary techniques of pharmacological-challenge functional magnetic resonance imaging (phMRI) and immediate-early gene activity. Areas of interest demonstrate a drug interaction when the CB1 receptor inverse agonist, rimonabant, is co-administered. This analysis highlights the corticostriatal-hypothalamic pathway, which is central to the motivational drive to eat.
Dodd
G T
GT
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, UK.
Stark
J A
JA
McKie
S
S
Williams
S R
SR
Luckman
S M
SM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D002186:Cannabinoids / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D004347:Drug Interactions; D004435:Eating / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology; D006963:Hyperphagia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D000077285:Rimonabant
D002186:Cannabinoids; D002491:Central Nervous System Agents; D003511:Cyclohexanols; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant; D010100:Oxygen