Abstract
A 40 base polymorphism of a variable number of tandem repeats (VNTR) has been described in the 3' untranslated region of the gene (SLC6A3) coding for the dopamine transporter (DAT). Despite being located in the untranslated region of the gene, this polymorphism has been associated with clinical phenotypes associated with dysregulation of dopamine transmission, such as attention deficit hyperactivity disorder and cocaine-induced paranoia. To examine the neurochemical phenotype associated with this polymorphism, we compared amphetamine-induced dopamine release (measured as displacement of the radiotracer [123I]IBZM) and DAT expression (measured with [123I]beta-CIT) in the striatum with Single Photon Computerized Emission Tomography (SPECT). Our sample included 59 subjects, 31 healthy controls and 29 patients with schizophrenia. No significant association was found between VNTR polymorphism and amphetamine-induced dopamine release or DAT density in the total sample, nor when each diagnostic group was considered separately. Thus, we did not replicate the findings of two previous studies, which had suggested that the 9 repeat allele was associated with either an increased or decreased DAT expression, albeit in different patient populations.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Amphetamine / administration & dosage
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Amphetamine / adverse effects
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Attention Deficit Disorder with Hyperactivity / genetics
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Attention Deficit Disorder with Hyperactivity / metabolism
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Attention Deficit Disorder with Hyperactivity / physiopathology
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Benzamides / pharmacokinetics
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cocaine / analogs & derivatives
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Cocaine / pharmacokinetics
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Cocaine-Related Disorders / genetics
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Cocaine-Related Disorders / metabolism
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Cocaine-Related Disorders / physiopathology
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Dopamine / metabolism*
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Dopamine Antagonists / pharmacokinetics
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Dopamine Plasma Membrane Transport Proteins
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Genotype
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Humans
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Iodine Radioisotopes / pharmacokinetics
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Membrane Glycoproteins*
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Membrane Transport Proteins*
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Minisatellite Repeats / genetics*
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Neostriatum / drug effects
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Neostriatum / metabolism*
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Neostriatum / physiopathology
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Nerve Tissue Proteins*
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Phenotype
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Polymorphism, Genetic / genetics*
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Psychotic Disorders / genetics
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Psychotic Disorders / metabolism
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Psychotic Disorders / physiopathology
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Pyrrolidines / pharmacokinetics
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Radiopharmaceuticals / pharmacokinetics
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Schizophrenia / genetics
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Schizophrenia / metabolism
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Schizophrenia / physiopathology
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Tomography, Emission-Computed, Single-Photon
Substances
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Benzamides
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Carrier Proteins
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Dopamine Antagonists
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Dopamine Plasma Membrane Transport Proteins
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Iodine Radioisotopes
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Pyrrolidines
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Radiopharmaceuticals
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SLC6A3 protein, human
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2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
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3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
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Amphetamine
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Cocaine
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Dopamine