title: On the behavioural specificity of hypophagia induced in male rats by mCPP, naltrexone, and their combination.
abstract: BACKGROUND
  Serotonergic (5-hydroxytryptamine, 5-HT) and opioidergic mechanisms are intimately involved in appetite regulation.
  
  
  OBJECTIVE
  In view of recent evidence of positive anorectic interactions between opioid and various non-opioid substrates, our aim was to assess the behavioural specificity of anorectic responses to the opioid receptor antagonist naltrexone, the 5-HT2C/1B receptor agonist mCPP and their combination.
  
  
  METHODS
  Behavioural profiling techniques, including the behavioural satiety sequence (BSS), were used to examine acute drug effects in non-deprived male rats tested with palatable mash. Experiment 1 characterised the dose-response profile of mCPP (0.1-3.0 mg/kg), while experiment 2 assessed the effects of combined treatment with a sub-anorectic dose of mCPP (0.1 mg/kg) and one of two low doses of naltrexone (0.1 and 1.0 mg/kg).
  
  
  RESULTS
  Experiment 1 confirmed the dose-dependent anorectic efficacy of mCPP, with robust effects on intake and feeding-related measures observed at 3.0 mg/kg. However, that dose was also associated with other behavioural alterations including increased grooming, reductions in locomotion and sniffing, and disruption of the BSS. In experiment 2, naltrexone dose-dependently reduced food intake and time spent feeding, effects accompanied by a behaviourally selective acceleration in the BSS. However, the addition of 0.1 mg/kg mCPP did not significantly alter the behavioural changes observed in response to either dose of naltrexone given alone.
  
  
  CONCLUSIONS
  In contrast to recently reported positive anorectic interactions involving low-dose combinations of opioid receptor antagonists or mCPP with cannabinoid CB1 receptor antagonists, present results would not appear to provide any support for potentially clinically relevant anorectic interactions between opioid and 5-HT2C/1B receptor mechanisms.
authors.affiliation: Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: F L
authors.initials: FL
authors.lastname: Wright
authors.forename: R J
authors.initials: RJ
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D006120:Grooming / Q000187:drug effects; D006185:Habituation, Psychophysiologic; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D012528:Satiety Response / Q000187:drug effects; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009292:Narcotic Antagonists; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D009271:Naltrexone; C015068:1-(3-chlorophenyl)piperazine