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Summary: Research Report
Lateral hypothalamic orexin/hypocretin neurons: A role in
reward-seeking and addiction
Gary Aston-Jones, Rachel J. Smith, Gregory C. Sartor, David E. Moorman, Lema Massi,
Pouya Tahsili-Fahadan, Kimberlei A. Richardson
Department of Neurosciences, Medical University of South Carolina, Basic Science Building 403, 173 Ashley Ave, MSC 510, Charleston,
SC 29425-5100, USA
A R T I C L E I N F O A B S T R A C T
Article history:
Accepted 29 September 2009
Available online 6 October 2009
Orexins (synonymous with hypocretins) are recently discovered neuropeptides made
exclusively in hypothalamus. Behavioral, anatomical, and neurophysiological studies show
that a subset of these cells, specifically those in lateral hypothalamus (LH), are involved in
reward processing and addictive behaviors. Fos expression in LH orexin neurons varied in
proportion to conditioned place preference (CPP) for morphine, cocaine, or food. This
relationship occurred both in drug-naïve rats and in animals during protracted morphine
withdrawal, when drug preference was elevated but food preference was decreased. Inputs to
the LH orexin cell field from lateral septum and bed nucleus of the stria terminalis were Fos-
activated during cocaine CPP in proportion to the preference expressed in each animal. This
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