title: Reversal of sibutramine-induced anorexia with a selective 5-HT(2C) receptor antagonist.
abstract: BACKGROUND
  The monoamine reuptake inhibitor sibutramine reduces food intake but the receptor subtypes mediating the effects of sibutramine on feeding remain to be clearly identified.
  
  
  OBJECTIVE
  The involvement of the 5-HT(2C) receptor subtype in the satiety-enhancing effects of sibutramine was investigated by examining the effects of co-administration of sibutramine with the selective 5-HT(2C) receptor antagonist SB 242084
  
  
  METHODS
  Microstructural analyses of licking for a glucose solution by non-deprived, male rats were performed over a range of doses of sibutramine to identify a selective satiety-enhancing dose (experiment 1). Similar analyses were performed after administration of a vehicle control, two doses of SB 242084 alone or two doses of SB 242084 in combination with sibutramine (experiment 2).
  
  
  RESULTS
  Sibutramine at doses of 1-3 mg/kg selectively reduced glucose consumption via a reduction in the number of bouts of licking. Non-selective effects to increase latency to lick were only observed at the higher dose of 6 mg/kg. Co-administration of sibutramine (3 mg/kg) with SB 242084 (1 or 3 mg/kg) reversed the effect of sibutramine on bout number whereas either dose of SB 242084 alone had no significant effect.
  
  
  CONCLUSIONS
  We confirm behaviourally selective effects of sibutramine on feeding and provide further support for the satiety-enhancing effects of sibutramine. Our data also provide evidence for the involvement of the 5-HT(2C) receptor in the satiety-enhancing effects of sibutramine although additional targets may have an impact, and further investigation of the molecular mechanisms underlying the efficacy of sibutramine as an anorectic is warranted.
authors.affiliation: School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. s.higgs.1@bham.ac.uk
authors.forename: Suzanne
authors.initials: S
authors.lastname: Higgs
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Cooper
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Barnes
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D001067:Appetite Depressants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003503:Cyclobutanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D001067:Appetite Depressants; D003503:Cyclobutanes; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; C058254:sibutramine