F L Wright1, R J Rodgers. 1. Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds, LS2 9JT, UK, England.
Abstract
RATIONALE: 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. OBJECTIVES: 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. CONCLUSION: 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.
RATIONALE: 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. OBJECTIVES: 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. CONCLUSION: 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: Frank L Greenway; M J Whitehouse; Maria Guttadauria; James W Anderson; Richard L Atkinson; Ken Fujioka; Kishore M Gadde; Alok K Gupta; Patrick O'Neil; Donald Schumacher; Diane Smith; Eduardo Dunayevich; Gary D Tollefson; Eckard Weber; Michael A Cowley Journal: Obesity (Silver Spring) Date: 2008-11-06 Impact factor: 5.002
Authors: Ben Jones; Teresa Buenaventura; Nisha Kanda; Pauline Chabosseau; Bryn M Owen; Rebecca Scott; Robert Goldin; Napat Angkathunyakul; Ivan R Corrêa; Domenico Bosco; Paul R Johnson; Lorenzo Piemonti; Piero Marchetti; A M James Shapiro; Blake J Cochran; Aylin C Hanyaloglu; Asuka Inoue; Tricia Tan; Guy A Rutter; Alejandra Tomas; Stephen R Bloom Journal: Nat Commun Date: 2018-04-23 Impact factor: 14.919
Authors: Daniel I Brierley; Marie K Holt; Arashdeep Singh; Alan de Araujo; Molly McDougle; Macarena Vergara; Majd H Afaghani; Shin Jae Lee; Karen Scott; Calyn Maske; Wolfgang Langhans; Eric Krause; Annette de Kloet; Fiona M Gribble; Frank Reimann; Linda Rinaman; Guillaume de Lartigue; Stefan Trapp Journal: Nat Metab Date: 2021-02-15