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Orexin-1 Receptor and Stress-Induced Relapse PDF Print E-mail
Poster Presentation by Jemma Richards at the Keystone Symposium: Neurobiology of Addiction, Santa Fe, New Mexico, Feb 28 - Mar 1.

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Abstract
Orexin-A is a hypothalamic peptide that acts via orexin type 1 (OX-1) receptors found extensively throughout the CNS. Orexins have been widely implicated in the central control of feeding, arousal and sleep. However, over the past few years, research has shown the orexin system to play an important role in reward, learning and addictive behaviors (Harris and Aston-Jones, 2005, 2006; Boutrel et al., 2005; Borgland et al., 2006). Specifically, orexin has been shown to be an important factor in mediating behaviors such as motivational drive produced by drugs of abuse such as cocaine, morphine and nicotine (DiLeone et al. 2003; Paneda et al. 2005). The aim of the current study was to determine whether orexin-A, via the OX-1 receptor, would be able to modulate ethanol-mediated behaviors. We studied the role of orexin-A in a voluntary consumption paradigm as well as in operant self administration and stress-induced reinstatement. Here we show that SB334867 (0-10mg/kg i.p.), the orexin-A receptor antagonist, does not reduce ethanol consumption in the voluntary 2 bottle choice paradigm however significantly inhibits operant self-administration of 10% ethanol and yohimbine-induced reinstatement in ethanol-experienced animals. These results suggest that orexin-A is involved in pathways controlling motivational drive to seek and consume ethanol but it is not necessary for voluntary consumption. Further the ability of the antagonist SB334867 to inhibit a yohimbine-induced reinstatement suggests OX-1 receptors may be activated under stress-like conditions, potentially to strengthen or reinforce environmental “cues” that were previously associated with a self-administered reward causing the reinstatement behavior.

Support Contributed By: State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (UCSF) to S.E.B. and Department of Defense to S.E.B.