title: Systemic ghrelin and reward: effect of cholinergic blockade.
abstract: OBJECTIVE
  Ghrelin is one of the most potent orexigens known to date. Recent data suggested that ghrelin is involved in reward-mediated processes such as the rewarding value of food. Whereas the neuronal pathways by which ghrelin regulates energy balance are well described, those involved in ghrelin-induced reward are still confusing. Therefore, we attempted to delineate the involvement of physiological and pharmacological rises in plasma ghrelin in the modulation of food reward seeking behaviours, using the classical conditioned place preference (CPP) procedure in C57BL6J mice, as well as in mice lacking the ghrelin receptor (GHSR1a -/-). We also determined whether these effects on reward-related behaviours could be partly mediated by cholinergic pathways by pre-treating mice with mecamylamine.
  
  
  RESULTS
  Upon moderate caloric restriction, systemic ghrelin levels increased from 108 ± 21 to 148 ± 39 pg/ml in C57BL6J mice and from 111 ± 24 to 179 ± 41 pg/ml in GHSR1a-null mice. Short exposure to rewarding food elicited a strong CPP and stimulation of locomotor activity in GHSR1a wild-type and C57BL6J mice. Conversely, the GHSR1a -/- mice did not exhibit such a food CPP, despite a negative energy balance. Pharmacological rise in systemic ghrelin further increased the time spent in the food-paired side with a higher CPP score (+71%) and this effect was blunted after cholinergic blockade by mecamylamine.
  
  
  CONCLUSIONS
  The ghrelin receptor is obligatory to acquire a food-CPP. The level of plasma ghrelin during conditioning determines the strength of food-induced reward seeking behaviours. The cholinergic pathway partly mediates the further enhancement of food reward induced by pharmacological rises in plasma ghrelin, but not that induced by physiological increases in ghrelin.
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland. emmanuel.disse@gmail.com
authors.forename: E
authors.initials: E
authors.lastname: Disse
authors.forename: A L
authors.initials: AL
authors.lastname: Bussier
authors.forename: N
authors.initials: N
authors.lastname: Deblon
authors.forename: P T
authors.initials: PT
authors.lastname: Pfluger
authors.forename: M H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: M
authors.initials: M
authors.lastname: Laville
authors.forename: F
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D000818:Animals; D031204:Caloric Restriction / Q000379:methods; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008464:Mecamylamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D012201:Reward
chemical_list: D054439:Ghrelin; D018733:Nicotinic Antagonists; D008464:Mecamylamine