title: Behavioural profile of exendin-4/naltrexone dose combinations in male rats during tests of palatable food consumption.
abstract: BACKGROUND
  The glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 potently suppresses food intake in animals and humans. However, little is known about the behavioural specificity of this effect either when administered alone or when co-administered with another anorectic agent.
  
  
  OBJECTIVE
  The present study characterises the effects of exendin-4, both alone and in combination with naltrexone, on behaviours displayed by male rats during tests with palatable mash.
  
  
  METHODS
  Experiment 1 examined the dose-response effects of exendin-4 (0.025-2.5 μg/kg, IP), while experiment 2 profiled the effects of low-dose combinations of the peptide (0.025 and 0.25 μg/kg) and naltrexone (0.1 mg/kg).
  
  
  RESULTS
  In experiment 1, exendin-4 dose dependently suppressed food intake as well as the frequency and rate of eating. However, these effects were accompanied by dose-dependent reductions in all active behaviours and, at 2.5 μg/kg, a large increase in resting and disruption of the behavioural satiety sequence (BSS). In experiment 2, while exendin-4 (0.25 μg/kg) and naltrexone each produced a significant reduction in intake and feeding behaviour (plus an acceleration in the BSS), co-treatment failed to produce stronger effects than those seen in response to either compound alone.
  
  
  CONCLUSIONS
  Similarities between the behavioural signature of exendin-4 and that previously reported for the emetic agent lithium chloride would suggest that exendin-4 anorexia is related to the aversive effects of the peptide. Furthermore, as low-dose combinations of the peptide with naltrexone failed to produce an additive/synergistic anorectic effect, this particular co-treatment strategy would not appear to have therapeutic significance.
authors.affiliation: Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds, LS2 9JT, UK, England.
authors.forename: F L
authors.initials: FL
authors.lastname: Wright
authors.forename: R J
authors.initials: RJ
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001067:Appetite Depressants; D010455:Peptides; D014688:Venoms; D009271:Naltrexone; D000077270:Exenatide