Imaging D2 Receptor Occupancy by Endogenous Dopamine in Humans

Laruelle, Marc; D’Souza, Cyril; Baldwin, Ronald M.; Abi‐Dargham, Anissa; Kanes, Stephen; Fingado, Christine L; Seibyl, John; Zoghbi, Sami S.; Bowers, Malcolm B.; Jatlow, Peter; Charney, Dennis S.; Innis, Robert B.

doi:10.1016/s0893-133x(97)00043-2

Cited by 251 publications

(210 citation statements)

References 45 publications

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“…However, these changes are thought to reflect aMPT-induced decreases in synaptic DA levels. Autoradiography studies in rats indicate that aMPT does not alter striatal DA D2 receptor K D or B max (Laruelle et al, 1997a). Fifth, catecholamines can affect cerebral blood flow, and the present results could reflect altered delivery or washout of the tracer.…”

Section: Discussionmentioning

confidence: 53%

“…Fourth, the increased [ 11 C]raclopride BP on the APTD test session might have reflected an upregulation of DA D2 receptors. aMPT increases striatal binding of [ 11 C]raclopride (Verhoeff et al, 2001), [ 123 I]IBZM (Laruelle et al, 1997a), and [ 123 I]epidepride (Fujita et al, 2000). However, these changes are thought to reflect aMPT-induced decreases in synaptic DA levels.…”

Section: Discussionmentioning

confidence: 99%

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Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Leyton

Dagher

Boileau

et al. 2003

Neuropsychopharmacol

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Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [ 11 C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [ 11 C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [ 11 C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t ¼ 4.2, equivalent to po0.05, Bonferroni corrected) and a priori identified regions of interest from each individual's coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [ 11 C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t ¼ 6.31; x ¼ À25, y ¼ À8, and z ¼ 0.1). In the t-map defined cluster, [ 11 C]raclopride BP values were 11.8 7 11.9% higher during the APTD session (po0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r ¼ À0.82, po0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Leyton

Dagher

Boileau

et al. 2003

Neuropsychopharmacol

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“…Acute dopamine depletion is possible in humans via administration of the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Challenges with AMPT have been successfully employed in conjunction with PET to estimate endogenous dopamine levels at D 2/3 R in living humans (Caravaggio et al, 2015;Caravaggio et al, 2014;Kegeles et al, 2010;Laruelle et al, 1997;Martinez et al, 2009;Verhoeff et al, 2001). Thus, measuring glutamate concentrations with 1 H-MRS before and after AMPT administration could help elucidate how dopamine depletion alters glutamatergic functioning in healthy persons and persons with neuropsychiatric diseases.…”

Section: Future Directions and Limitationsmentioning

confidence: 99%

“…However, a negative correlation was observed between glutamate concentrations in the left prefrontal cortex and dopamine synthesis capacity in the left ventral striatum (r 2 = .17). Future PET studies examining dopamine synthesis capacity or endogenous dopaminergic tone (Caravaggio et al, 2014;Laruelle et al, 1997;Verhoeff et al, 2001) should also examine glutamate concentrations measured with 1 H-MRS in the dorsal striatum and cortex; in healthy persons and persons with neuropsychiatric diseases.…”

Section: Introductionmentioning

confidence: 99%

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Caravaggio

Nakajima

Plitman

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Understanding the interplay between the neurotransmitters dopamine and glutamate in the striatum has become the highlight of several theories of neuropsychiatric illnesses, such as schizophrenia. Using in vivo brain imaging in humans, alterations in dopamine and glutamate concentrations have been observed in several neuropsychiatric disorders. However, it is unclear a priori how alterations in striatal dopamine should modulate glutamate concentrations in the basal ganglia. In this selective mini-review, we examine the consequence of reducing striatal dopamine functioning on glutamate concentrations in the striatum and cortex; regions of interest heavily examined in the human brain imaging studies. We examine the predictions of the classical model of the basal ganglia, and contrast it with findings in humans and animals. The review concludes that chronic dopamine depletion (>4 months) produces decreases in striatal glutamate levels which are consistent with the classical model of the basal ganglia. However, acute alterations in striatal dopamine functioning, specifically at the D2 receptors, may produce opposite affects. This has important implications for models of the basal ganglia and theorizing about neurochemical alterations in neuropsychiatric diseases. Moreover, these findings may help guide a priori hypotheses for 1H-MRS studies measuring glutamate changes given alterations in dopaminergic functioning in humans.

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“…DA levels during stimulant-induced release have been estimated by comparing radiotracer binding at baseline and after amphetamine or methylphenidate challenges using PET and the DA D 2 receptor (D 2 R) radiotracer [ 11 C]raclopride (Volkow et al 1994;Breier et al 1997) as well as SPECT and (Booij et al 1997;Abi-Dargham et al 1998). DA levels during baseline release have been estimated by comparing radiotracer binding at baseline and after a rapid DA depletion induced by the competitive and reversible tyrosine hydroxylase inhibitor ␣ -methyl-para-tyrosine (AMPT) (Engelman et al 1968) using SPECT and [ 123 I]IBZM (Laruelle et al 1997;Abi-Dargham et al 2000) or [ 123 I]epidepride (Fujita et al 2000).…”

mentioning

confidence: 99%

A Simple Method to Measure Baseline Occupancy of Neostriatal Dopamine D2 Receptors by Dopamine In Vivo in Healthy Subjects

Verhoeff

Kapur

Hussey

et al. 2001

Neuropsychopharmacology

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Imaging D2 Receptor Occupancy by Endogenous Dopamine in Humans

Cited by 251 publications

References 45 publications

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

A Simple Method to Measure Baseline Occupancy of Neostriatal Dopamine D2 Receptors by Dopamine In Vivo in Healthy Subjects

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