Dose-response effects of orexin-A on food intake and the bahavioural satiety sequence in rats

Although intracerebroventricular (i.c.v.) administration of orexin-A has be en reported to stimulate food intake and/or feeding behaviour in rats, mice and goldfish, little attention has thus far been paid to its effects on no rmal patterns of feeding. In the present study, a continuous monitoring tec hnique was used to characterise the effects of this novel neuropeptide on t he microstructure of rat behaviour during a 1-h test with palatable wet mas h. Particular attention was devoted to the behavioural satiety sequence, in which feeding is followed by grooming and resting. Although results confir med the hyperphagic effects of orexin-A (3.33-30.0 mug i.c.v.), gross behav ioural analysis failed to reveal any reliable effects of peptide treatment on eating, drinking, sniffing, grooming, resting, locomotion or rearing. Ho wever, microstructural analysis revealed behavioural effects of orexin-A th at are both dose- and time-dependent. At lower doses (3.33-10.0 mug), orexi n-A primarily delayed behavioural satiety, i.e. the normal transition from eating to resting. In contrast, the 30 mug dose initially induced a sedativ e-like effect, significantly suppressing eating and other active behaviours for the first 15-20 min of the test period. This sedative-like effect resu lted in a phase-shifting of the entire behavioural sequence with higher tha n control levels of eating, grooming, locomotion, rearing and sniffing obse rved over the second half of the test session. Present findings illustrate the advantages of microstructural behavioural analysis and suggest that the hyperphagic response to low doses of orexin-A results largely from a delay in behavioural satiety while that seen in response to high doses may occur in rebound to initial behavioural suppression. Further studies will be req uired to confirm the identity of the specific orexin receptors (i.e. OX1 or OX2) involved in mediating the dose-dependent behavioural effects reported . (C) 2000 Elsevier Science B.V. All rights reserved.