Journal Article

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

Richards, Jemma K., Bartlett, Selena E., Taha, Sharif A., Borgland, Stephanie L., Steensland, Pia, Bonci, Antonello, Simms, Jeffrey A.

2008

Overview

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.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Adrenergic alpha-Antagonists - pharmacology / Alcoholism - physiopathology / Animal behavior / Animals / Benzoxazoles - pharmacology / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Conditioning, Operant - drug effects / Dose-Response Relationship, Drug / Ethanol / Extinction, Psychological - drug effects / Food / Male / Medical sciences / Motivation / Motor Activity - drug effects / Neurosciences / Neurotransmitters / Orexin Receptors / Original Investigation / Pharmacology/Toxicology / Psychiatry / Psychopharmacology / Psychotropic drugs / Rats / Rats, Long-Evans / Receptors, G-Protein-Coupled - antagonists & inhibitors / Receptors, Neuropeptide - antagonists & inhibitors / Rodents / Self Administration / Sucrose - administration & dosage / Sugar / Taste - drug effects / Taste - physiology / Urea - analogs & derivatives / Urea - pharmacology / Yohimbine - pharmacology