D-serine facilitates the effectiveness of extinction to reduce drug-primed reinstatement of cocaine-induced conditioned place preference
Open accessAbstract
Addiction is a disease that is characterized by compulsive drug-seeking and use despite negative health and social consequences. One obstacle in treating addiction is a high susceptibility for relapse which persists despite prolonged periods of abstinence. Relapse can be triggered by drug predictive stimuli such as environmental context and drug associated cues, as well as the addictive drug itself. The conditioned place preference (CPP) behavioral model is a useful paradigm for studying the ability of these drug predictive stimuli to reinstate drug-seeking behavior. The present study investigated the dose-dependent effects of D-serine (10 mg/kg, 30 mg/kg and 100 mg/kg) on extinction training and drug-primed reinstatement in cocaine-conditioned rats. In the first experiment, D-serine had no effect on the acquisition or development of cocaine-induced locomotor sensitization or CPP. In the second experiment, D-serine treatment resulted in significantly decreased time spent in the drug-paired compartment following completion of an extinction protocol. A cocaine-primed reinstatement test indicated that the combination of extinction training along with D-serine treatment resulted in a significant reduction of drug-seeking behavior. The third experiment assessed D-serine's long-term effects to diminish drug-primed reinstatement. D-serine treatment given during extinction was effective in reducing drug-seeking for more than four weeks of abstinence after the last cocaine exposure. These findings demonstrate that D-serine may be an effective adjunct therapeutic agent along with cognitive behavioral therapy for the treatment of cocaine addiction. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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Exogenous D-serine treatment reverts impaired plasticity and reduces behavioral manifestations associated with cocaine addiction, including cocaine-induced place preference, reinstatement of cocaine self-administration, and locomotor sensitization to cocaine.
“In keeping, exogenous D-serine treatment reverts the impaired plasticity and reduces a number of behavioral manifestations associated to cocaine addiction, including cocaine-induced place preference 121, 122 , reinstatement of cocaine self-administration (relapse) 123 and locomotor sensitization to cocaine 120, 121 .”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [122]
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- Authors
- Hammond, S., Seymour, C. M., Burger, A., & Wagner, J. J.
- Affiliations
- University of Georgia (US)
- Corresponding author
- Wagner, John J.
- ORCID
- Wagner, John J.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 64
- Pages
- 464-471
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3445779
- OpenAlex
- W2062959060
- Cited by
- 32
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 2
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (DA016302)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- D-serine, cocaine dependence, extinction training, conditioned place preference, relapse, drug-seeking behavior, nootropic drugs, cognitive behavioral therapy, glutamate modulators, locomotor sensitization
- MeSH terms
- Animals, Antimetabolites, Behavior, Animal, Cocaine, Combined Modality Therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Extinction, Psychological, Male, Serine, Spatial Behavior, Stereoisomerism, Cognitive Behavioral Therapy, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Excitatory Amino Acid Agonists, Nootropic Agents, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Rats, Secondary Prevention, Drug-Seeking Behavior
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