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Orexin-1 receptor antagonism decreases ethanol consumption and preference selectively in high-ethanolepreferring
 

Summary: Orexin-1 receptor antagonism decreases ethanol consumption
and preference selectively in high-ethanolepreferring
SpragueeDawley rats
David E. Moorman, Gary Aston-Jones*
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Suite 403-BSB, MSC 510, Charleston, SC 29425, USA
Received 24 March 2009; received in revised form 8 June 2009; accepted 2 July 2009
Abstract
Work from our laboratory has shown that orexin (ORX; or hypocretin) neurons in the lateral hypothalamus are involved in preference for
morphine, cocaine, and food. Other groups have demonstrated a connection between the ORX system and ethanol-related behaviors. Here, we
extended those results to investigate, in outbred SpragueeDawley rats, the relationship between ethanol preference and the ORX system. In
Experiment 1, rats were trained to drink 10% ethanol using the intermittent access (IA) technique. In Experiment 2, different groups of rats were
trained to drink 10% ethanol using either IA or the sucrose-fade (SF) technique. Following ethanol-drinking acquisition, ethanol preferencewas
assessed using two-bottle-choice tests. The rats were then tested for changes in preference with additional two-bottle-choice tests following
administration of the orexin-1 receptor antagonist SB-334867 (SB; 30 mg/kg, intraperitoneally). Differences in ethanol preference were
observed across individuals, with a significantly higher ethanol preference observed in rats trained to drink using IA compared with SF. In both
Experiments 1 and 2, SB reduced ethanol preference selectively in rats with high ethanol preference. These results demonstrate a strong, causal
relationship between the ORX system and ethanol preference in outbred rats. These findings provide additional evidence that the ORX system
provides opportunities to develop novel treatments for alcohol abuse. 2009 Elsevier Inc. All rights reserved.
Keywords: Orexin; Lateral hypothalamus; Alcohol; Reward; Preference
Introduction

  

Source: Aston-Jones, Gary - Department of Neurosciences, Medical University of South Carolina

 

Collections: Biology and Medicine