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Updated: Jun 21, 2026
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Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats
Published on: October 5, 2021
Orexin/hypocretin is necessary for context-driven cocaine-seeking.
Rachel J Smith1, Pouya Tahsili-Fahadan, Gary Aston-Jones
1Department of Neurosciences, Medical University of South Carolina, 173 Ashley Ave., 403 Basic Science Bldg., Charleston, SC 29425-5100, USA.
Neuropharmacology
|July 14, 2009
Summary
Orexin 1 receptor (OX1R) signaling is crucial for cocaine-seeking behavior triggered by drug-associated cues after abstinence or extinction. Blocking OX1R with SB-334867 significantly reduced this conditioned relapse.
Area of Science:
- Neuroscience
- Addiction Research
- Pharmacology
Background:
- Orexin/hypocretin system plays a role in addiction and relapse.
- The orexin 1 receptor (OX1R) is a key target for understanding drug-seeking behaviors.
Purpose of the Study:
- To investigate the role of the orexin system, specifically OX1R, in cocaine-seeking behavior.
- To determine if OX1R antagonism affects conditioned cocaine-seeking after abstinence or extinction.
Main Methods:
- Rats underwent chronic cocaine self-administration followed by extinction training or abstinence.
- The OX1R antagonist SB-334867 was administered before re-exposure to the drug-associated context.
- Cocaine-seeking behavior was measured upon re-exposure to the environment.
Main Results:
- SB-334867 significantly reduced cocaine-seeking behavior in rats.
- This attenuation occurred after both short-term (1 day) and long-term (2 weeks) abstinence.
- The antagonist was also effective following extinction of seeking behavior in a different environment.
Conclusions:
- Orexin signaling at OX1R is essential for conditioned cocaine-seeking behavior.
- Blocking OX1R can reduce relapse triggered by drug-associated cues, irrespective of abstinence or extinction status.
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