A septal-hypothalamic pathway drives orexin neurons, which is necessary for conditioned cocaine preference

Gregory C. Sartor, Gary S. Aston-Jones

Research output: Contribution to journalArticle

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4623-4631
Number of pages9
JournalJournal of Neuroscience
Volume32
Issue number13
DOIs
StatePublished - Mar 28 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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