Cited by 4,733Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.

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Di Chiara, G, Imperato, A·1988·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.85.14.5274

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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
Published
1988-07
Volume
85
Issue
14
Pages
5274-5278
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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