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Psychopharmacology (Berl). 2008 Jul;199(1):109-17. doi: 10.1007/s00213-008-1136-5. Epub 2008 May 10.

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats.

Author information

1
Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.

Abstract

RATIONALE:

Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking.

MATERIALS AND METHODS:

Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test.

RESULTS:

The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test.

CONCLUSIONS:

The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

PMID:
18470506
PMCID:
PMC2668563
DOI:
10.1007/s00213-008-1136-5
[Indexed for MEDLINE]
Free PMC Article

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