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Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.
Open accessAbstract
The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused.
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“Limitations for this study include the fact that we recorded from the dorsal striatum and not from the nucleus accumbens, which is an area implicated in drug reward (Di Chiara and Imperato, 1988; Koob and Bloom, 1988).”
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Leitl, M. D., Onvani, S., Bowers, M. S., Cheng, K., Rice, K. C., Carlezon, W. A., Banks, M. L., & Negus, S. S. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.236 · Cited by 87
Greenwell, T. N., Funk, C. K., Cottone, P., Richardson, H. N., Chen, S. A., Rice, K. C., Zorrilla, E. P., & Koob, G. F. (2009) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00142.x · Cited by 87
Metadata
- Authors
- Di Chiara, G., & Imperato, A.
- Affiliations
- Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1988-07
- Volume
- 85
- Issue
- 14
- Pages
- 5274-5278
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC281732
- OpenAlex
- W2165398609
- Cited by
- 4,733
- References
- 27
- Citations by year
- 2026: 62 · 2025: 104 · 2024: 78 · 2023: 112 · 2022: 141 · 2021: 133 · 2020: 160 · 2019: 155 · 2018: 162 · 2017: 141 · 2016: 183 · 2015: 173 · 2014: 194 · 2013: 193 · 2012: 163
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- drug abuse, extracellular dopamine, mesolimbic system, nucleus accumbens septi, dopamine release, hypermotility, hypomotility, kappa opioid receptor agonists, U50,488, tifluadom, bremazocine, haloperidol, imipramine, atropine, diphenhydramine, opiates, ethanol, nicotine, amphetamine, cocaine, limbic system
- MeSH terms
- Ethanol, Amphetamine, Animals, Caudate Nucleus, Cocaine, Dopamine, Homovanillic Acid, Kinetics, Male, Narcotics, Nicotine, Nucleus Accumbens, Rats, Inbred Strains, Receptors, Opioid, Septal Nuclei, Illicit Drugs, Synapses, Antipsychotic Agents, 3,4-Dihydroxyphenylacetic Acid, Receptors, Opioid, mu, Receptors, Opioid, kappa, Rats
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