Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by prior experience with (+)-amphetamine: a microdialysis study in freely moving rats
Abstract
In humans the repeated use of amphetamine (AMPH) produces a hypersensitivity to the psychotogenic effects of AMPH that persists for months to years after the cessation of drug use. To explore the neurobiological basis of this phenomenon the long-term effects of dextroamphetamine [+)-AMPH) on brain monoamines and behavior were studied in an animal model of AMPH psychosis. An escalating dose pretreatment regimen (from 1 to 10 mg/kg over 5 weeks) was used to mimic the pattern of drug use associated with the development of addiction and AMPH psychosis. The effect of pretreatment with AMPH on dopamine (DA) release in the ventral striatum (nucleus accumbens) was determined by measuring the extracellular concentrations of DA and DA metabolites using in vivo microdialysis, both before and after an AMPH challenge. The postmortem tissue concentrations of DA, serotonin and their metabolites were measured to determine if this treatment was neurotoxic. Escalating doses of (+)-AMPH were not neurotoxic, and 25-30 days after the cessation of drug treatment animals showed relatively normal levels of spontaneous motor activity across the day-night cycle. However, AMPH pretreatment produced robust behavioral sensitization. Animals showed a marked hypersensitivity to the motor stimulant effects of an AMPH challenge, even after 15-20 days of withdrawal. Most importantly, this hyperdopaminergic behavioral syndrome was accompanied by significantly elevated DA release in the ventral striatum. In contrast, AMPH pretreatment had no effect on the basal extracellular concentrations of DA.(ABSTRACT TRUNCATED AT 250 WORDS)
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Repeated peaks of mesolimbic dopamine release lead to brain neuroadaptations, in particular, sensitization of these dopamine-related systems.
“Together these repeated peaks of mesolimbic dopamine release lead to brain neuroadaptations, in particular, sensitization of these dopamine-related systems (T. E. Robinson & Becker, 1986; T. E. Robinson, Jurson, Bennett, & Bentgen, 1988).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as T. E. Robinson, Jurson, Bennett, & Bentgen, 1988
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- Authors
- Robinson, T. E., Jurson, P. A., Bennett, J. A., & Bentgen, K. M.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Robinson, Terry E.
- ORCID
- Robinson, Terry E.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1988-10
- Volume
- 462
- Issue
- 2
- Pages
- 211-222
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1982383406
- Cited by
- 463
- References
- 50
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 11
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institute on Drug Abuse (DA 04294)
- National Institute of Neurological Disorders and Stroke (NS 00844)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- amphetamine, nucleus accumbens, ventral striatum, dopamine release, behavioral sensitization, drug-induced psychosis, serotonin, neurotoxicity, drug withdrawal, addiction
- MeSH terms
- Amphetamine, Animals, Dialysis, Dopamine, Dose-Response Relationship, Drug, Female, Homovanillic Acid, Motor Activity, Synaptic Transmission, Nucleus Accumbens, Septal Nuclei, Serotonin, 3,4-Dihydroxyphenylacetic Acid, Rats
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