Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats
Richards, Jemma, Simms, Jeffrey, Steensland, Pia, Taha, Sharif, Borgland, Stephanie, Bonci, Antonello, & Bartlett, Selena (2008) Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats. Psychopharmacology, 199(1), pp. 109-117.
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.
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|Item Type:||Journal Article|
|Keywords:||Orexin, Hypocretin, Operant self administration, Reinstatement, Yohimbine, SB334867, Stress, Ethanol|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PHARMACOLOGY AND PHARMACEUTICAL SCIENCES (111500)
Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000) > PSYCHOLOGY (170100)
Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000) > COGNITIVE SCIENCE (170200)
|Deposited On:||24 Aug 2011 22:17|
|Last Modified:||29 Feb 2012 14:35|
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