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Br J Pharmacol. 2008 May;154(2):406-16. doi: 10.1038/bjp.2008.3. Epub 2008 Jan 28.

Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high-fat food self-administration and reinstatement of food seeking in rats.

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1
Behavioral Neuroscience Branch, NIDA/IRP/NIH/DHHS, Baltimore, MD 21224, USA.

Abstract

BACKGROUND AND PURPOSE:

Many studies have demonstrated a role of hypocretin 1 (orexin 1) receptors in home-cage food consumption in rodents. However, the role of these receptors in operant food self-administration or relapse to food seeking in animal models is unknown.

EXPERIMENTAL APPROACH:

In Experiment 1, we trained food-restricted rats (16-20 g per day) to lever press for high-fat (35%) pellets (3-6 h per day, every other day). We then tested the effect of the hypocretin 1 receptor antagonist SB 334867 (10, 20 mg kg(-1), i.p) on pellet self-administration. In Experiment 2, we trained rats to self-administer the food pellets, and following extinction of the food-reinforced responding, we tested the effect of hypocretin 1 (3 and 6 mug, i.c.v) on reinstatement of food-seeking and the effect of SB 334867 on this reinstatement. In Experiment 3, we tested the effect of SB 334867 on reinstatement induced by non-contingent pellet exposure (pellet-priming) or the pharmacological stressor yohimbine (2 mg kg(-1), i.p).

KEY RESULTS:

SB 334867 attenuated high-fat pellet self-administration. In contrast, SB 334867 had no effect on reinstatement of lever presses induced by hypocretin 1, pellet-priming or yohimbine.

CONCLUSIONS AND IMPLICATIONS:

These data indicate that during dieting, hypocretin 1 receptors contribute to operant high-fat pellet self-administration, but not to relapse to food seeking induced by acute re-exposure to the food itself or by the induction of a stress-like state.

PMID:
18223663
PMCID:
PMC2442445
DOI:
10.1038/bjp.2008.3
[Indexed for MEDLINE]
Free PMC Article
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