title: The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature.
abstract: OBJECTIVE
  Significant weight gain is a problematic side effect of treatment with the antipsychotic drug olanzapine (OLA). Previous studies in rats suggest that one of the contributing factors is an impairment in satiation that results in increased food intake. However, the mechanisms underlying this impairment in satiation remain largely unclear.
  
  
  RESULTS
  In this study, we determined the effect of OLA on levels of leptin, insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1, peptide YY and amylin in male rats that had received a fixed amount of food. OLA did not affect the secretion of any of these hormones, except for ghrelin levels, which were increased compared with controls. Furthermore, when ghrelin levels were determined in rats just before they received their meal, OLA caused a significant increase in ghrelin levels compared with controls, whereas OLA failed to affect baseline ghrelin levels. Next, we investigated the effect of OLA on the efficacy of CCK to reduce meal size. With coadministration, OLA pretreatment counteracted the reduction in meal size by CCK, although there was no significant interaction between the treatments. Finally, telemetry measurements revealed that acute OLA treatment causes a temporary decrease in both locomotor activity and body core temperature.
  
  
  CONCLUSIONS
  Taken together, this study shows that acute injection of OLA selectively increases meal-related ghrelin secretion and this may partially underlie the impairment in satiation by OLA.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: van der Zwaal
authors.forename: M
authors.initials: M
authors.lastname: Merkestein
authors.forename: Y K
authors.initials: YK
authors.lastname: Lam
authors.forename: M A D
authors.initials: MA
authors.lastname: Brans
authors.forename: M C M
authors.initials: MC
authors.lastname: Luijendijk
authors.forename: L I H
authors.initials: LI
authors.lastname: Bok
authors.forename: E R
authors.initials: ER
authors.lastname: Verheij
authors.forename: S E
authors.initials: SE
authors.lastname: la Fleur
authors.forename: R A H
authors.initials: RA
authors.lastname: Adan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D002766:Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D004435:Eating; D054439:Ghrelin / Q000187:drug effects* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D000077152:Olanzapine; D019894:Peptide YY / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012527:Satiation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D054439:Ghrelin; D058228:Islet Amyloid Polypeptide; D019894:Peptide YY; D001569:Benzodiazepines; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D000077152:Olanzapine