Viral restoration of dopamine to the nucleus accumbens is sufficient to induce a locomotor response to amphetamine
Abstract
Administration of amphetamine to mice evokes hyperlocomotion. Dopamine deficient (DD) mice, in which tyrosine hydroxylase (TH) has been specifically inactivated in dopaminergic neurons, have a blunted response to amphetamine, indicating that the hyperlocomotive response requires dopamine. Dopamine production can be restored to specific brain regions by using adeno-associated viruses expressing TH and GTP cyclohydrolase 1 (GTPCH1). Restoration of dopamine specifically to the nucleus accumbens (NAc) of DD mice completely restores the ability of these mice to respond to amphetamine. This response is specific to the dopamine production in the NAc, as restoration of dopamine production to the caudate putamen (CPu) does not fully restore the hyperlocomotive response to amphetamine. These data support previous studies in which accumbal dopamine is required for producing a normal locomotor response to amphetamine and further show that release of dopamine restricted to the NAc is sufficient for this response
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Dopamine deficient mice display heightened locomotion when treated with psychomotor stimulants if dopamine is selectively restored in the ventral striatum, but not the dorsal striatum.
“Dopamine deficient mice display heightened locomotion when treated with psychomotor stimulants if dopamine is selectively restored in the ventral striatum, but not the dorsal striatum (Heusner et al., 2003)”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Heusner et al., 2003
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- Authors
- Heusner, C. L., Hnasko, T. S., Szczypka, M. S., Liu, Y., During, M. J., & Palmiter, R. D.
- Affiliations
- University of Washington (US)
- Thomas Jefferson University (US)
- University of Auckland (NZ)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Palmiter, Richard D.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 980
- Issue
- 2
- Pages
- 266-274
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2095555089
- Cited by
- 48
- References
- 31
- Citations by year
- 2026: 1 · 2024: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2t32da007278-31)
- National Institute on Drug Abuse (T32-DA07278)
- 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
- amphetamine, hyperlocomotion, dopamine, nucleus accumbens, caudate-putamen, tyrosine hydroxylase, GTP cyclohydrolase I, adeno-associated virus, gene therapy, dopamine deficiency, dopaminergic neurons, locomotor response
- MeSH terms
- Dependovirus, Amphetamine, Animals, Dopamine, Genetic Vectors, Humans, Motor Activity, Nucleus Accumbens, Recombination, Genetic, Genetic Therapy, Mice
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