A Septal-Hypothalamic Pathway Drives Orexin Neurons, Which Is Necessary for Conditioned Cocaine Preference
Open accessAbstract
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.
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The LS is necessary for the formation of cocaine conditioned place preference in rats.
“is necessary for the formation of cocaine conditioned place preference in rats [36,37].”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [37]
In Results, Experiment 3 (page unavailable), rats were conditioned before the rostral lateral septum (LSr) was inactivated, and inactivation before the CPP test attenuated cocaine preference. The Discussion describes the LSr pathway as critical for the expression of preference. These findings support a role in expressing cocaine CPP, but do not establish that the LS is necessary for its formation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe lateral septum plays a key role in modulating context-specific motivational states.
“and the lateral septum plays a key role in modulating context-specific motivational states (Sheehan et al., 2004; Luo et al., 2011; Sartor and Aston-Jones, 2012).”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Sartor and Aston-Jones, 2012
The LS is part of the brain reward system.
“other studies indicating that the LS is part of the brain reward system.”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [37]
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Research works printed but not linked: 50
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- Authors
- Sartor, G. C., & Aston-Jones, G. S.
- Affiliations
- Medical University of South Carolina (US)
- ORCID
- Sartor, Gregory C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-03-28
- Volume
- 32
- Issue
- 13
- Pages
- 4623-4631
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3350779
- OpenAlex
- W2060257902
- Cited by
- 109
- References
- 56
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 10 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 14 · 2017: 10 · 2016: 10 · 2015: 7 · 2014: 12 · 2013: 5 · 2012: 7
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute on Drug Abuse (R37DA006214, R37-DA06214, R01DA017289, T32DA007288)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- orexin neurons, lateral hypothalamus, lateral septum, cocaine conditioned place preference, drug-seeking behavior, reward systems, Fos expression, baclofen, muscimol, morpholino antisense
- MeSH terms
- Orexins, Animals, Baclofen, Benzoxazoles, Cocaine, Conditioning, Psychological, Hypothalamus, Male, Microinjections, Muscimol, Naphthyridines, Neural Pathways, Neurons, Neuropeptides, Urea, Rats, Sprague-Dawley, Septum of Brain, Intracellular Signaling Peptides and Proteins, Rats, Neuroanatomical Tract-Tracing Techniques, Drug-Seeking Behavior, Morpholinos
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