Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats
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RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.
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Hcrt-1 receptor antagonist blocked stress-induced reinstatement of alcohol seeking.
“An Hcrt-1 receptor antagonist also blocked the stress (yohimbine)induced reinstatement of alcohol seeking(Richards et al., 2008).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Richards et al., 2008
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- Authors
- Richards, J. K., Simms, J. A., Steensland, P., Taha, S. A., Borgland, S. L., Bonci, A., & Bartlett, S. E.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Bartlett, Selena E.
- Venue
- Psychopharmacology
- Published
- 2008-05-10
- Volume
- 199
- Issue
- 1
- Pages
- 109-117
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC2668563
- OpenAlex
- W2164595661
- Cited by
- 234
- References
- 56
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 12 · 2017: 9 · 2016: 13 · 2015: 15 · 2014: 23 · 2013: 17 · 2012: 26
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Psychopharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (W81XWH)
- University of California, San Francisco
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- orexin-1 receptor, SB-334867, yohimbine, ethanol self-administration, sucrose self-administration, reinstatement, locomotor activity, Long-Evans rats
- MeSH terms
- Adrenergic alpha-Antagonists, Alcoholism, Animals, Benzoxazoles, Conditioning, Operant, Dose-Response Relationship, Drug, Extinction, Psychological, Male, Motivation, Motor Activity, Naphthyridines, Self Administration, Sucrose, Taste, Urea, Yohimbine, Receptors, Neuropeptide, Rats, Long-Evans, Receptors, G-Protein-Coupled, Rats, Orexin Receptors
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