Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson’s disease

Kaasinen, Valtteri; Någren, Kjell; Hietala, Jarmo; Oikonen, Vesa; Vilkman, Harry; Farde, Lars; Halldin, Christer; Rinne, Juha O.

doi:10.1212/wnl.54.7.1482

Cited by 112 publications

(66 citation statements)

References 45 publications

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“…analysis of the same anterior cingulate cortex ROIs provided plausible binding potential values which were in agreement with previous research (Suhara et al 2002;Hagelberg et al 2004;Talvik et al 2003;Kaasinen et al 2000). Based on the consistent response of the data to the MRTM2 analysis, but not to the Logan model analysis, it was conjectured that high levels of noise were present in the anterior cingulate cortex.…”

Section: Figuresupporting

confidence: 87%

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Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Pryweller¹

2006

VURJ

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Five adult rhesus monkeys with a history of prenatal cocaine exposure (PNCE) region was implemented in the PMOD software package to determine ligand binding potentials for D2/D3 receptors and dopamine transporters (DAT) in each of the ROIs to test whether fallypride and/or FECNT binding potentials, measures of D2/D3 and DAT levels respectively, were influenced by prenatal cocaine exposure. Preliminary results suggest a trend of reduced D2/D3 binding potential with increased PNCE, but future research is necessary.Despite some variability amongst individual studies, a consensus is emerging that prenatal cocaine exposure (PNCE) can have dose dependent effects on the development of dopaminergic circuits . A range of impairments, including deficits in recognition memory, processing speed, task persistence, arousal, distractibility, and stress-responsiveness, have been reported in infants and children exposed to cocaine in utero (Azuma et

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Section: Figuresupporting

confidence: 87%

“…The BP values of D2 receptors in the ACC of the control monkeys were on the higher end of reported BP ranges, but still comparable (Suhara et al 2002;Hagelberg et al 2004;Talvik et al 2003;Kaasinen et al 2000). …”

Section: Effect Of Prenatal Cocaine Exposurementioning

confidence: 65%

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Pryweller¹

2006

VURJ

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“…The PD with PG group was taking lower chronic DA agonist doses, along with compensatory increases in levodopa doses, in order to retain benefit to PD symptoms. Since both DA agonists and levodopa effect DA receptor expression (Chernoloz et al, 2009;Kaasinen et al, 2000;Pitts et al, 1995;Subramaniam et al, 1992;Thobois et al, 2004) we chose to match groups on total LEDD, but it must be acknowledged that these differences may have influenced our results.…”

Section: Discussion [11c] Flb-457 Bp In the Midbrainmentioning

confidence: 99%

“…For example, two patients with PG were no longer using DA agonists, and the remainder had DA agonists reduced, with concomitant increases in levodopa (Table 2). Thus, we considered it more important to match patients for total levodopa equivalent doses rather than either levodopa or DA agonists, since both may have an impact on DA receptor expression (Chernoloz et al, 2009;Kaasinen et al, 2000;Pitts et al, 1995;Subramaniam et al, 1992;Thobois et al, 2004).…”

Section: Participants and Experimental Designmentioning

confidence: 99%

Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson's patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

Ray

Miyasaki

Zurowski

et al. 2012

Neurobiology of Disease

121

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Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson's disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait.

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“…However, contemporary studies have revealed that the projections of neurons within the midline/intralaminar complex are specific for distinct forebrain targets Groenewegen, 1990, 1991;Moga et al, 1995;Turner and Herkenham, 1991), and have challenged the concept of 'nonspecificity' of these nuclei (Groenewegen and Berendse, 1994). The midline/intralaminar nuclei have figured prominently both in recent post-mortem and imaging studies and in theoretical considerations of the pathophysiology of schizophrenia (Andreasen, 1997;Buchsbaum et al, 1996;Byne et al, 2002;Cohen and Yurgelun-Todd, 2001;Deutch et al, 1995;Popken et al, 2000) addictive disorders (Staley and Mash, 1996;Volkow et al, 1996Volkow et al, , 1997Wang et al, 1997;Yousef et al, 1995), and Parkinson's disease (PD) (Feigin et al, 2002;Filion, 2000;Freeman et al, 2001;Henderson et al, 2000;Hershey et al, 1998;Kaasinen et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Distribution of Dopamine D2-Like Receptors in the Human Thalamus: Autoradiographic and PET Studies

Rieck

Ansari

Whetsell

et al. 2003

Neuropsychopharmacol

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The distribution of dopamine (DA) D 2 -like receptors in the human thalamus was studied using in vitro autoradiographic techniques and in vivo positron emission tomography in normal control subjects. [ 125 I]Epidepride, which binds with high affinity to DA D 2 and D 3 receptors, was used in autoradiographic studies to determine the distribution and density of D 2 -like receptors, and the epidepride analogue [ 18 F]fallypride positron was used for positron emission tomography studies to delineate D 2 -like receptors in vivo. Both approaches revealed a heterogeneous distribution of thalamic D 2/3 receptors, with relatively high densities in the intralaminar and midline thalamic nuclei, including the paraventricular, parataenial, paracentral, centrolateral, and centromedian/parafascicular nuclei. Moderate densities of D 2/3 sites were seen in the mediodorsal and anterior nuclei, while other thalamic nuclei expressed lower levels of D 2 -like receptors. Most thalamic nuclei that express high densities of D 2 -like receptors project to forebrain DA terminal fields, suggesting that both the thalamic neurons expressing D 2 -like receptors and the projection targets of these neurons are regulated by DA. Because the midline/intralaminar nuclei receive prominent projections from both the ascending reticular activating core and the hypothalamus, these thalamic nuclei may integrate activity conveying both interoceptive and exteroceptive information to telencephalic DA systems involved in reward and cognition.

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Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson’s disease

Abstract: These results imply that the D2/3 receptor subtypes outside the striatum are affected in advanced PD but not in the early stages of the disease, and that this receptor decline is present in the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus.

Cited by 112 publications

References 45 publications

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson's patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

Distribution of Dopamine D2-Like Receptors in the Human Thalamus: Autoradiographic and PET Studies

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