A Septal-Hypothalamic Pathway Drives Orexin Neurons, Which Is Necessary for Conditioned Cocaine Preference
Open Access
- 28 March 2012
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 32 (13), 4623-4631
- https://doi.org/10.1523/jneurosci.4561-11.2012
Abstract
Orexins (also called hypocretins) have been shown to be importantly involved in reward and addiction, but little is known about the circuitry that regulates orexin neuronal activity during drug-seeking behaviors. Here, we examined inputs to the lateral hypothalamus (LH) orexin cell field from the lateral septum (LS) using tract-tracing and Fos immunohistochemistry after cocaine (10 mg/kg) conditioned place preference (CPP) in Sprague Dawley rats. We found that neurons in rostral LS (LSr) that project to LH are Fos-activated in proportion to cocaine CPP, and that inhibition of LSr neurons with local baclofen and muscimol microinjection (0.3/0.03 nmol) blocks expression of Fos in LH orexin cells and cocaine preference. In addition, using local inactivation in LS and orexin antisense morpholinos in LH, we found that LSr influences on LH orexin neurons are critical for the expression of cocaine preference. These results indicate that LSr activates LH orexin neurons during cocaine place preference, and that this circuit is essential for expression of cocaine place preference.Keywords
This publication has 54 references indexed in Scilit:
- The role of the dynorphin–κ opioid system in the reinforcing effects of drugs of abusePsychopharmacology, 2010
- Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitizationBrain Research, 2010
- Orexin-1 receptor antagonism decreases ethanol consumption and preference selectively in high-ethanol–preferring Sprague–Dawley ratsAlcohol, 2009
- Orexin/hypocretin signaling at the orexin 1 receptor regulates cue‐elicited cocaine‐seekingEuropean Journal of Neuroscience, 2009
- Orexin/hypocretin is necessary for context-driven cocaine-seekingNeuropharmacology, 2009
- The melanin-concentrating hormone system modulates cocaine rewardProceedings of the National Academy of Sciences of the United States of America, 2009
- Activation of orexin/hypocretin projections to basal forebrain and paraventricular thalamus by acute nicotineBrain Research Bulletin, 2008
- Lateral hypothalamic orexin neurons are critically involved in learning to associate an environment with morphine rewardBehavioural Brain Research, 2007
- Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioningLearning & Memory, 2007
- The orexin system regulates alcohol‐seeking in ratsBritish Journal of Pharmacology, 2006