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Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine

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Kuczenski, R, Segal, DS, Cho, AK, Melega, W·1995·The Journal of Neuroscience

DOI 10.1523/jneurosci.15-02-01308.1995PMC PMC6577819

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Abstract

Microdialysis in behaving animals was used to concomitantly characterize the dopamine and 5-HT responses in the caudate and the norepinephrine response in the hippocampus to the D- and L-isomers of amphetamine and methamphetamine. Doses of all four drugs which promoted similar stereotypy responses produced a D-amphetamine-like response profile of dopamine and dopamine metabolites, suggesting that all these drugs interact with dopamine systems to facilitate the release of transmitter. However, in contrast to the similar behavioral profiles, the magnitude of the dopamine responses diverged significantly. In addition, all four drugs increased extracellular norepinephrine and 5-HT, but the relative responses differed markedly from dopamine and from each other. The contrasting structure-activity relationships for these drugs likely reflect their differential potency at the various neuronal uptake transporters in promoting either transmitter release, and/or uptake blockade. In addition, the interaction of each drug at the vesicular transporters, as well as the availability of a cytoplasmic pool of transmitter likely also contribute to the neurotransmitter response. Because of the particularly divergent transmitter response profiles exhibited by L-methamphetamine, its behavioral and neurotransmitter effects were characterized over a more extended range of doses. Although the duration of the increase in extracellular dopamine was clearly proportional to dose, the dose-dependent increases in the magnitude of the dopamine response did not parallel the behavioral profiles. The results of these studies indicate that, while the dopamine, norepinephrine and 5-HT responses to these drugs probably contribute to the expression of stimulant-induced behaviors, simple relationships between the neurotransmitter responses and the behavioral profiles were not evident.

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In Vivo Measurement of Dopamine and Its Metabolites by Intracerebral Dialysis: Changes After d‐Amphetamine
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Authors: Kuczenski, R., Segal, D., Cho, A., & Melega, W.
Affiliations: UC San Diego Health System (US)
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1995-02-01
Volume: 15
Issue: 2
Pages: 1308-1317
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.15-02-01308.1995
PMC: PMC6577819
OpenAlex: W1934404972
Cited by: 376
References: 44
Citations by year: 2026: 2 · 2025: 3 · 2024: 2 · 2023: 11 · 2022: 10 · 2021: 13 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 11 · 2016: 9 · 2015: 9 · 2014: 24 · 2013: 18 · 2012: 22
FWCI: 3.33
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01da002411-13, 5r01da004157-14)
U.S. Public Health Service
National Institute on Drug Abuse (DA-01568, DA 02411, DA04157, R01DA001568)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: methamphetamine, d-amphetamine, stereotypy, dopamine release, noradrenaline release, serotonin release, caudate nucleus, hippocampus, vesicular transporters, structure-activity relationship, microdialysis
MeSH terms: Amphetamine, Animals, Behavior, Animal, Caudate Nucleus, Dopamine, Hippocampus, Methamphetamine, Norepinephrine, Serotonin, Stereoisomerism, Stereotyped Behavior, Microdialysis, Neurotransmitter Agents, Rats

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Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine

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