Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine
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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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Amphetamine increases synaptic levels of monoamines (dopamine, noradrenaline and serotonin) by increasing their release through a reversal of the monoamine transporters, primarily the catecholamine transporters.
“AMP increases the synaptic levels of monoamines (dopamine, noradrenaline and serotonin) by increasing their release through a reversal of the monoamine transporters, primarily the catecholamine transporters (see Fleckenstein et al., 2007; Hutson et al., 2014, for review; Kuczenski et al., 1995; Sulzer et al., 2005).”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Kuczenski et al., 1995
The Microdialysis section reports increased extracellular dopamine, norepinephrine, and serotonin after amphetamine or methamphetamine. The Discussion describes carrier-mediated release as a possible mechanism for dopamine and serotonin, but says norepinephrine uptake blockade predominates at low doses and release becomes prominent at higher doses. It does not establish transporter reversal—primarily through catecholamine transporters—as the general mechanism claimed. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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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
- 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
- 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 › 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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