The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for these peptides in the reinforcing properties of most drugs of abuse. Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain structures implicated in the regulation of arousal, stress, and reward. Although Orx/Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be a key relay of Orx/Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of the “drug addiction circuitry,” an increasing amount of evidence demonstrated that the PVT—particularly PVT Orx/Hcrt transmission—was implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. The present review discusses recent findings that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of abuse may promote persistent compulsive drug-seeking behavior following a period of protracted abstinence and as such may represent a relevant target for understanding the long-term vulnerability to drug relapse after withdrawal.
Keywords: paraventricular nucleus of the thalamus, orexin, hypocretin, drug-seeking behavior, natural reward
Citation: Martin-Fardon R and Boutrel B (2012) Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry? Front. Behav. Neurosci. 6:75. doi: 10.3389/fnbeh.2012.00075
Received: 16 August 2012; Paper pending published: 13 September 2012;
Accepted: 19 October 2012; Published online: 09 November 2012.
Edited by:Luis De Lecea, Stanford University School of Medicine, USA
Reviewed by:Gregg Stanwood, Vanderbilt University, USA
Copyright © 2012 Martin-Fardon and Boutrel. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Rémi Martin-Fardon, Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2120, La Jolla, CA 92037, USA. e-mail: firstname.lastname@example.org