Central cannabinoid signaling mediating food intake: a pharmacological-challenge magnetic resonance imaging and functional histology study in rat

Neuroscience. 2009 Nov 10;163(4):1192-200. doi: 10.1016/j.neuroscience.2009.07.022. Epub 2009 Jul 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Brain Mapping
  • Cannabinoids / metabolism*
  • Central Nervous System Agents / pharmacology
  • Cyclohexanols / pharmacology
  • Drug Interactions
  • Eating / physiology*
  • Genes, Immediate-Early / physiology
  • Hyperphagia / chemically induced
  • Hyperphagia / drug therapy
  • Hyperphagia / metabolism
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Oxygen / blood
  • Piperidines / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Rimonabant

Substances

  • Cannabinoids
  • Central Nervous System Agents
  • Cyclohexanols
  • Piperidines
  • Proto-Oncogene Proteins c-fos
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Rimonabant
  • Oxygen