The importance of acclimatisation and habituation to experimental conditions when investigating the anorectic effects of gastrointestinal hormones in the rat

Objective: Peptide YY3-36 (PYY3-36), glucagon-like peptide-1 (GLP-1), oxyntomodulin and cholecystokinin (CCK) are gastrointestinal-derived hormones that are released postprandially in proportion to the amount of calories ingested. All significantly reduce food intake following peripheral administration to rodents. We have investigated the effect of handling, exposure to a novel environment or to environmental enrichment on the anorectic effect of these gut hormones. Results: Results suggest that the transfer of a rat into a novel environment ( cage change) inhibits the anorectic response to peripherally administered PYY3-36 and oxyntomodulin (1 h food intake reduction (% saline control): PYY/ home cage 82.3 +/- 5.9%, P < 0.05; PYY/ clean cage 103.4 +/- 9.7%; oxyntomodulin/home cage 71.6712.1%, P < 0.05; oxyntomodulin/clean cage 103.0 +/- 8.5%) and attenuates the anorectic response to GLP-1 and CCK (1 h food intake reduction (% saline control): MTII/home cage 68.8 +/- 6.4%, P < 0.01; GLP-1/clean cage 80.0 +/- 9.3%; CCK/home cage 49.8 +/- 6.2%, P < 0.001; CCK/clean cage 69.4 +/- 10.6%, P < 0.05). We have also observed that exposure to a novel environment does not alter anorectic effect of peripherally administered melanocortin 3/4 receptor agonist, melanotan II ( MTII) ( 1 h food intake reduction (% saline control): MTII/home cage 32.0 +/- 6.3%, P < 0.001; MTII/clean cage 24.8 +/- 4.2%, P < 0.001). The attenuation in food intake observed following exposure to a novel environment can be attributed, in part, to a significant reduction in the food intake of the saline treated animals. In a further study, the anorectic effect of peripherally administered PYY3-36 is attenuated in unhandled rats (88 +/- 4.2% saline control, P=ns) or rats exposed to environmental enrichment (103.3 +/- 9.7% saline control, P=ns), but not in animals that were handled extensively prior to the study (80.1 +/- 7.3% saline control, P < 0.05). Conclusion: These studies highlight the importance of handling, acclimatisation and habituation of rodents to experimental conditions prior to investigating the ability of gut hormones to alter food intake.