Related Experiment Video
Updated: Aug 2, 2026
Operant Sensation Seeking in the Mouse
Published on: November 10, 2010
Satiety enhancement by selective orexin-1 receptor antagonist SB-334867: influence of test context and profile
Y Ishii1, J E Blundell, J C G Halford
1Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, LS2 9JT, UK.
Abstract:
Acute systemic treatment with the selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake in rats, an effect associated with an acceleration in behavioural satiety and unrelated to gross behavioural disruption, alterations in palatability, or toxicity. However, as enhanced satiety is behaviourally indexed by an earlier-than-normal transition from eating to resting, and since orexin-A has been implicated in mechanisms of arousal, it remains possible that sedation contributes to the anorectic effect of acute OX1R blockade. Previous work has shown that, when treated with SB-334867 (30 mg/kg, i.p.) 30 min before a 1h test with palatable food, rats begin to show appreciable levels of resting 10-15 min earlier than under control conditions (i.e. around 20 min versus 30-35 min into the session). The present results demonstrate that a 20 min increase in the injection-test interval (i.e. 50 min) had no significant impact on the anorectic, behavioural or weight gain effects of SB-334867 in non-deprived male rats. Most importantly, this altered treatment regimen led to a temporal profile of resting virtually identical to that previously observed with the more conventional 30 min injection-test interval. Although parallel studies indicated that the OX1R antagonist accelerated the onset of resting (and suppressed most active behaviours) even in the absence of food, an equianorectic dose of the natural satiety-related signal cholescystokinin octapeptide (CCK-8S; 5 microg/kg, i.p.) also produced very similar behavioural effects regardless of the presence of food. Together with evidence that SB-334867 preserves the structural integrity of natural feeding behaviour, does not induce nausea/illness or alter taste/palatability and fails to influence EEG measures of arousal/sleep, the present findings are consistent with the view that acute OX1R antagonism selectively enhances satiety. However, unlike the immediate short-circuiting of the satiety sequence induced by CCK-8S, the slower response to SB-334867 implies a more indirect mechanism of action.
Insights
Selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake by enhancing satiety, not sedation. This effect on appetite is consistent even with delayed administration, suggesting a direct impact on satiety mechanisms.
Area of Science:
- Neuroscience
- Pharmacology
- Physiology
Background:
- Orexin-1 receptor (OX1R) antagonists, like SB-334867, reduce food intake in rats.
- The anorectic effect may be linked to enhanced satiety or sedation, as OX1R signaling influences arousal.
- Previous studies showed SB-334867 accelerates resting behavior, a marker of satiety.
Purpose of the Study:
- To investigate if sedation contributes to the anorectic effects of SB-334867.
- To determine if altering the injection-test interval impacts SB-334867's effects on food intake, behavior, and weight gain.
- To compare the behavioral effects of SB-334867 with a known satiety signal, CCK-8S.
Main Methods:
- Rats were treated with SB-334867 (30 mg/kg, i.p.) at different injection-test intervals (30 min vs. 50 min).
- Food intake, resting behavior, and weight gain were monitored during a palatable food test.
- Behavioral effects were compared with those of cholecystokinin octapeptide (CCK-8S).
Main Results:
- Increasing the injection-test interval to 50 min did not alter the anorectic, behavioral, or weight gain effects of SB-334867.
- The temporal profile of resting behavior remained similar across different injection-test intervals.
- SB-334867 accelerated resting behavior even without food, similar to CCK-8S, but with a slower onset.
Conclusions:
- Acute OX1R antagonism selectively enhances satiety without causing sedation or disrupting natural feeding behavior.
- The findings support a direct role for OX1R in regulating satiety.
- SB-334867's slower action suggests a more indirect mechanism compared to CCK-8S.
