Amphetamine-Induced Displacement of [18F] Fallypride in Striatum and Extrastriatal Regions in Humans

Riccardi, Patrizia; Li, Rui; Ansari, M. Sib; Zald, David H.; Park, Sohee; Dawant, Benoît M.; Anderson, Sharlet; Doop, Mikisha L.; Woodward, Neil D.; Schoenberg, Evan D.; Schmidt, Dennis E.; Baldwin, Ronald M.; Kessler, Robert

doi:10.1038/sj.npp.1300916

Cited by 125 publications

(125 citation statements)

References 93 publications

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“…Although some loss of quantitation likely occurs in the current study, a partial volume correction was not used, as the exact borders of the substantia nigra are not well defined on high-resolution T1-weighted MRI scans. The identifiability of DA D 2 r levels in this structure when using a PET scanner with high resolution is supported by a number of observations, that is, low mean test-retest error of DA D 2 r levels for this structure-5.2% (Mukherjee et al, 2002) the high intersubject reliability for the substantia nigra we have reported in normal subjects-an 8% coefficient of variation across subjects (Riccardi et al, 2006), and the high correlation between PET […”

Section: Discussionmentioning

confidence: 62%

Occupancy of Striatal and Extrastriatal Dopamine D2 Receptors by Clozapine and Quetiapine

Kessler

Ansari

Riccardi

et al. 2006

Neuropsychopharmacol

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117

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Clozapine and quetiapine have a low incidence of extrapyramidal side effects at clinically effective doses, which appears to be related to their significantly lower occupancy of striatal dopamine D 2 receptors (DA D 2 r) compared to typical antipsychotic drugs (APDs). Animal studies have indicated that clozapine and quetiapine produce selective effects on cortical and limbic regions of the brain and in particular on dopaminergic neurotransmission in these regions. Previous PET and SPECT studies have reported conflicting results regarding whether clozapine produces preferential occupancy of cortical DA D 2 r. To examine whether clozapine and/or quetiapine produce preferential occupancy of DA D 2 r in cortex and limbic regions, we studied the occupancy of putamenal, ventral striatal, thalamic, amygdala, substantia nigra, and temporal cortical DA D 2 r using PET with [18 F]fallypride in six schizophrenic subjects receiving clozapine monotherapy and in seven schizophrenic subjects receiving quetiapine monotherapy. Doses were chosen clinically to minimize psychopathology at tolerable levels of side effects such as drowsiness. All had minimal positive symptoms at the time of the study. Regional receptor occupancies were estimated using mean regional DA D 2 r levels calculated for 10 off-medication schizophrenic subjects. Both clozapine and quetiapine produced lower levels of putamenal DA D 2 r occupancy than those reported for typical APDs, 47.8 and 33.5%, respectively. Clozapine produced preferential occupancy of temporal cortical vs putamenal DA D 2 r, 59.8% (p ¼ 0.05, corrected for multiple comparisons), and significantly lower levels of occupancy in the substantia nigra, 18.4% (p ¼ 0.0015, corrected for multiple comparisons). Quetiapine also produced preferential occupancy of temporal cortical DA D 2 r, 46.9% (p ¼ 0.03, corrected for multiple comparisons), but did not spare occupancy of substantia nigra DA D 2 r. The therapeutic effects of clozapine and quetiapine appear to be achieved at less than the 65% threshold for occupancy seen with typical APDs, consistent with the involvement of non-DA D 2 r mechanisms in at least partially mediating the therapeutic effects of these drugs. Preferential occupancy of cortical DA D 2 r, sparing occupancy of substantia nigra receptors, and non-DA D 2 r-mediated actions may contribute to the antipsychotic actions of these and other atypical APDs.

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Section: Discussionmentioning

confidence: 62%

Occupancy of Striatal and Extrastriatal Dopamine D2 Receptors by Clozapine and Quetiapine

Kessler

Ansari

Riccardi

et al. 2006

Neuropsychopharmacol

Self Cite

117

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“…The head was positioned to include imaging from the top of the striatum to the lower portions of the cerebellum and stabilized with a polyform plastic mask molded to the subject's head. Regional blood volume (rCBV) was measured using bolus inhalation of 556-1482 Bq of C 15 O [32], and regional blood flow (rCBF) was measured using bolus injection of 1111-1852 Bq of H 2 15 O [33,34]. At least 20 minutes was allowed for radioactive decay before injecting 185-259 Bq of [ 18 F]NMB intravenously over 30 seconds.…”

Section: Protocolmentioning

confidence: 99%

“…[ 11 C]Raclopride has greater selectivity compared to most radiolabeled analogs of spiperone [10,11,12], but is susceptible to displacement by endogenous dopamine [13,14] [15]. This susceptibility provides a useful strategy for measuring release of endogenous dopamine but complicates modeling and confounds interpretation of PET-based measurements of D 2 -like receptors.…”

Section: Introductionmentioning

confidence: 99%

Validation of the reference tissue model for estimation of dopaminergic D2-like receptor binding with [18F](N-methyl)benperidol in humans

Antenor-Dorsey

Markham

Moerlein

et al. 2008

Nuclear Medicine and Biology

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PET measurements of dopaminergic D 2 -like receptors may provide important insights into disorders such as Parkinson's disease, schizophrenia, dystonia and Tourette's syndrome. The PET radioligand [ 18 F] (N-Methyl)Benperidol ([ 18 F]-NMB) has high affinity and selectivity for D 2 -like receptors and is not displaced by endogenous dopamine. The goal of this study is to evaluate use of a graphical method utilizing a reference tissue region for ([ 18 F]-NMB PET analysis by comparisons to an explicit three-compartment tracer kinetic model and graphical method that use arterial blood measurements. We estimated binding potential (BP) in the caudate and putamen using all three methods in 16 humans and found that the three-compartment tracer kinetic method provided the highest BP estimates while the graphical method using a reference region yielded the lowest estimates (p<0.0001 by repeated measures ANOVA). However, the three methods yielded highly correlated BP estimates for the two regions of interest. We conclude that the graphical method using a reference region still provides a useful estimate of BP comparable to methods using arterial blood sampling, especially since the reference region method is less invasive and computationally more straightforward; thereby simplifying these measurements.

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“…Until now, work focused on assessing a potential relationship between extrastriatal DA characteristics and subjective responses has been limited due to 11 Craclopride and 123 I-IBZM's inability to reliably estimate DRD2/3 availability (measured as binding potential, BPnd) outside the striatum. The radiotracer 18 F-fallypride, however, is able to estimate DRD2/3 BPnd in PFC, temporal lobes, and the insula in addition to the striatum (Mukherjee et al, 2002;Riccardi et al, 2008) and can index DA release after damphetamine (dAMPH) administration, measured as %ΔBPnd from baseline (Riccardi et al, 2006a;Slifstein et al, 2010). We were particularly interested in using fallypride to test whether DA functions in paralimbic cortical areas, specifically the mPFC/OFC, related to subjective responses to dAMPH given past evidence that activity in these areas are increased in response to psychostimulants in drug naïve individuals (Vollm et al, 2004) and correlate with their self-reported euphoric effects (Udo de Haes et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Variability in paralimbic dopamine signaling correlates with subjective responses to D-amphetamine

Smith¹

2016

Intrinsic Act

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Subjective responses to psychostimulants vary, the basis of which is poorly understood, especially in relation to possible cortical contributions. Here, we tested for relationships between participants' positive subjective responses to oral d-amphetamine (dAMPH) versus placebo and variability in striatal and extrastriatal dopamine (DA) receptor availability and release, measured via positron emission tomography (PET) with the radiotracer 18 F-fallypride. Analyses focused on 35 healthy adult participants showing positive subjective effects to dAMPH measured via the Drug Effects Questionnaire (DEQ) Feel, Like, High, and Want More subscales (Responders), and were repeated after inclusion of 11 subjects who lacked subjective responses. Associations between peak DEQ subscale ratings and both baseline 18 F-fallypride binding potential (BPnd; an index of D2/D3 receptor availability) and the percentage change in BPnd post dAMPH (%ΔBPnd; a measure of DA release) were assessed. Baseline BPnd in ventromedial prefrontal cortex (vmPFC) predicted the peak level of High reported following dAMPH. Furthermore, %ΔBPnd in vmPFC positively correlated with DEQ Want More ratings. DEQ Want More was also positively correlated with %ΔBPnd in right ventral striatum and left insula. This work indicates that characteristics of DA functioning in vmPFC, a cortical area implicated in subjective valuation, are associated with both subjective high and incentive (wanting) responses. The observation that insula %ΔBPnd was associated with drug wanting converges with evidence suggesting its role in drug craving. These findings highlight the importance of variability in DA signaling in specific paralimbic cortical regions in dAMPH's subjective response, which may confer risk for abusing psychostimulants.

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Amphetamine-Induced Displacement of [18F] Fallypride in Striatum and Extrastriatal Regions in Humans

Cited by 125 publications

References 93 publications

Occupancy of Striatal and Extrastriatal Dopamine D2 Receptors by Clozapine and Quetiapine

Occupancy of Striatal and Extrastriatal Dopamine D2 Receptors by Clozapine and Quetiapine

Validation of the reference tissue model for estimation of dopaminergic D2-like receptor binding with [18F](N-methyl)benperidol in humans

Variability in paralimbic dopamine signaling correlates with subjective responses to D-amphetamine

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