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

• Published in: Psychopharmacologia Vol. 199; no. 1; pp. 109 - 117
• Main Authors: Richards, Jemma K., Simms, Jeffrey A., Steensland, Pia, Taha, Sharif A., Borgland, Stephanie L., Bonci, Antonello, Bartlett, Selena E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2008; Springer; Springer Nature B.V
• Subjects: 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; Operant self administration; Yohimbine; Ethanol; Reinstatement; Orexin; Hypocretin; Stress; SB334867; α2-Adrenergic receptor; Rat; Sucrose; Rodentia; Instrumental conditioning; Self administration; Neuropeptide; Vertebrata; Mammalia; Animal; Antagonist; Inhibition
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-008-1136-5

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.