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.