title: Oral administration of the 5-HT2Creceptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia.
abstract: BACKGROUND
  The 5-HT(2C) receptor subtype has been implicated extensively in the regulation of ingestive behaviour.
  
  
  OBJECTIVE
  To assess whether chronic administration of the preferential 5-HT(2C) receptor agonist, mCPP, reduces rat body weight gain and to determine if this effect is wholly or partially attributable to the effect of the drug on daily food intake.
  
  
  METHODS
  Animals were orally dosed with mCPP (10 mg/kg P.O., b.i.d.) or d-fenfluramine (2.5 mg/kg P.O., b.i.d.) for 28 days. Further groups of animals received drug treatments for the first 14 days and then received vehicle for the remainder of the experiment. Locomotor activity was assessed on days 2, 14, and 28. In a second study, animals received mCPP or d-fenfluramine for a 14-day period (dose and route were identical to the previous study). A group of pair-fed controls were included to determine whether the effects on body weight gain were attributable entirely to drug-induced hypophagia.
  
  
  RESULTS
  Both mCPP and d-fenfluramine reduced body weight relative to vehicle-treated controls over the 28-day period. Withdrawal of the drugs on day 14 resulted in a significant rebound weight gain. Neither mCPP nor d-fenfluramine induced significant changes in locomotor activity compared to controls on any of the days tested (2, 14 or 28). In the second, 14-day study, changes in the body weights of pair-fed controls closely paralleled those of their drug-treated counterparts.
  
  
  CONCLUSIONS
  These data indicate that chronic oral treatment with mCPP and d-fenfluramine significantly reduces rat body weight gain, an effect that is reversible upon withdrawal and wholly attributable to maintained hypophagia.
authors.affiliation: Vernalis Research Limited, Oakdene Court, Winnersh, Wokingham, UK. S.Vickers@vernalis.com
authors.forename: S P
authors.initials: SP
authors.lastname: Vickers
authors.forename: N
authors.initials: N
authors.lastname: Easton
authors.forename: L J
authors.initials: LJ
authors.lastname: Webster
authors.forename: A
authors.initials: A
authors.lastname: Wyatt
authors.forename: M J
authors.initials: MJ
authors.lastname: Bickerdike
authors.forename: C T
authors.initials: CT
authors.lastname: Dourish
authors.forename: G A
authors.initials: GA
authors.lastname: Kennett
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes / Q000662:veterinary; D004435:Eating / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D005277:Fenfluramine; C015068:1-(3-chlorophenyl)piperazine