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

Verhoeff, Nicolaas Paul L.G.; Kapur, Shitij; Hussey, Doug; Lee, M; Christensen, Bruce K.; C.Psych,; Papatheodorou, George; Zipursky, Robert B.

doi:10.1016/s0893-133x(01)00231-7

Cited by 67 publications

(81 citation statements)

References 52 publications

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“…For example, aMPT requires repeated administration and a minimum of 3 days in-hospital observation (Verhoeff et al, 2001); its administration can induce crystalluria (Brogden et al, 1981) and acute dystonic reactions (McCann et al, 1990). In comparison, APTD can induce measurable effects within 3 h Figure 3 Correlation between plasma levels of tyrosine, following phenylalanine/tyrosine depletion, and the ability of d-amphetamine to elicit DA release.…”

Section: Discussionmentioning

confidence: 99%

“…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: 99%

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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“…In a D 2 ligand-binding PET study using 11 C-raclopride in healthy volunteers, AMPT impaired attention, which was associated with increased raclopride binding potential, whereas psychomotor speed remained unchanged. 102 This study did not include a placebo condition, but can nevertheless be taken to indicate that the effects of AMPT on cognitive performance are associated with lowered DA function. Another study reported decreased performance on memory and attention tasks relative to lactose administration when AMPT was followed by 40 h sleep deprivation, but the effects were not significant after AMPT or sleep deprivation alone.…”

Section: Acute Tryptophan Depletionmentioning

confidence: 99%

Monoamine depletion in psychiatric and healthy populations: review

2003

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A number of techniques temporarily lower the functioning of monoamines: acute tryptophan depletion (ATD), alpha-methyl-para-tyrosine (AMPT) and acute phenylalanine/tyrosine depletion (APTD). This paper reviews the results of monoamine depletion studies in humans for the period 1966 until December 2002. The evidence suggests that all three interventions are specific, in terms of their short-term effects on one or two neurotransmitter systems, rather than on brain protein metabolism in general. The AMPT procedure is somewhat less specific, affecting both the dopamine and norepinephrine systems. The behavioral effects of ATD and AMPT are remarkably similar. Neither procedure has an immediate effect on the symptoms of depressed patients; however, both induce transient depressive symptoms in some remitted depressed patients. The magnitude of the effects, response rate and quality of response are also comparable. APTD has not been studied in recovered major depressive patients. Despite the similarities, the effects are distinctive in that ATD affects a subgroup of recently remitted patients treated with serotonergic medications, whereas AMPT affects recently remitted patients treated with noradrenergic medications. The evidence also suggests that ATD and APTD affect different cognitive functions, in particular different memory systems. Few studies investigated cognitive effects of the procedures in patients. Patients who are in remission for longer may also be vulnerable to ATD and AMPT, but the relationship with prior treatment is much weaker. For these patients, individual vulnerability markers are the more important determinants of depressive response, making these techniques potentially useful models of vulnerability to depression. Molecular Psychiatry (2003) 8, 951-973.

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

Abstract: The effect of endogenous dopamine (DA)

Cited by 67 publications

References 52 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

Monoamine depletion in psychiatric and healthy populations: review

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