Enhancement of in vivo binding of [123I]?-CIT by MK-801 in rat brain

Nakano, Takayuki; Takatoku, Keizo; Matoba, Yoshinori; Iwamoto, Bunichi; Nishiura, Masaru; Ito, Osamu

doi:10.1002/(sici)1098-2396(199812)30:4<402::aid-syn7>3.0.co;2-n

Cited by 8 publications

(6 citation statements)

References 53 publications

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“…Thus, microdialysis measures of increases in extracellular DA in response to PCP might reflect spillover secondary to monoamine transporter blockade at higher doses (Schiffer et al, 2001a), while lower doses of PCP may be absent from this effect. In fact, recent findings using MK-801 have provided evidence that this drug increases the availability of DAT sites (Nakano et al, 1998;Page et al, 2000;Schiffer et al, 2001b;Kagawa et al, 2002). Taken together, it appears that individual NMDA antagonists might produce compound-specific effects on striatal dopaminergic systems as a function of their affinity for targets outside the NMDA receptor complex.…”

Section: Discussionmentioning

confidence: 98%

Positron Emission Tomography Studies of Potential Mechanisms Underlying Phencyclidine-Induced Alterations in Striatal Dopamine

Schiffer

Logan

Dewey

2003

Neuropsychopharmacol

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Positron emission tomography (PET), in combination with 11 C-raclopride, was used to examine the effects of phencyclidine (PCP) on dopamine (DA) in the primate striatum. In addition, we explored the hypotheses that GABAergic pathways as well as molecular targets beyond the N-methyl-D-aspartate (NMDA) receptor complex (ie dopamine transporter proteins, DAT) contribute to PCP's effects. In the first series of experiments, 11 C-raclopride was administered at baseline and 30 min following intravenous PCP administration. In the second series of studies, g-vinyl GABA (GVG) was used to assess whether enhanced GABAergic tone altered NMDA antagonistinduced changes in DA. Animals received an initial PET scan followed by pretreatment with GVG (300 mg/kg), then PCP 30 min prior to a second scan. Finally, we explored the possible contributions of DAT blockade to PCP-induced increases in DA. By examining 11 Ccocaine binding a paradigm in which PCP was coadministered with the radiotracer, we assessed the direct competition between these two compounds for the DAT. At 0.1, 0.5, and 1.0 mg/kg, PCP decreased 11 C-raclopride binding by 2.1, 14.9 7 2.2 and 8.18 7 1.1%, respectively. These effects were completely attenuated by GVG (3.38 7 3.1% decrease in 11 C-raclopride binding). Finally, PCP (0.5 mg/ kg) decreased 11 C-cocaine binding by 25.5 7 4.3%, while at 1.0 mg/kg this decrease was 13.5%, consistent with a competitive interaction at the DAT. These results suggest that PCP may be exerting some direct effects through the DAT and that GABA partially modulates NMDA-antagonist-induced increases in striatal DA.

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Section: Discussionmentioning

confidence: 98%

Positron Emission Tomography Studies of Potential Mechanisms Underlying Phencyclidine-Induced Alterations in Striatal Dopamine

Schiffer

Logan

Dewey

2003

Neuropsychopharmacol

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“…Nevertheless, investigation of the modulating effects of ketamine may prove a better strategy to detect NMDA activity than direct DA release. ↑ 26% (Nakano et al, 1998) B is bolus, RTM is reference tissue model, AIKM is arterial input kinetic model, Graphical is Logan plot. Dose of ketamine is given as a sum of initial bolus ϩthe infusion rate ϭtotal amount administered.…”

Section: Future Directionsmentioning

confidence: 99%

Imaging of striatal dopamine release elicited with NMDA antagonists: is there anything there to be seen?

Rabiner

2007

J Psychopharmacol

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Increased release of striatal dopamine, indexed with in vivo imaging of the D(2) receptor, has been reported following an acute challenge with N-methyl-D-aspartate (NMDA) antagonist ketamine in humans. Replications of this result have not been consistently successful. The aim of this manuscript is to evaluate in vivo imaging examination of NMDA antagonism on striataL dopamine release in published reports of humans and pre-clinical species. The literature is evaluated in conjunction with insights on the effect of NMDA antagonism on dopamine release, elicited from microdialysis and tissue turnover studies, and suggestions for future studies are made.

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“…But do endogenous neurotransmitters still have an influence on radiolabelled b-CIT binding? Binding characteristics of [ 123 I]b-CIT in rat brain have been shown to be altered by serotonin transporter inhibitor clomipramine (Fujita et al 1997) and by opiate agonist fentanyl as well as by N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (Nakano et al 1998). The release of dopamine from nigrostriatal axon terminals in the striatum is affected by stimulation of NMDA receptors, which provides support for the suggestion that these receptors are located on presynaptic nerve terminals and are able to influence transmitter release (Vizi 2000).…”

Section: Dopamine Transporter In Vivo Imagingmentioning

confidence: 99%

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

Bergström¹,

Tupala²,

Tiihonen³

2001

Pharmacology & Toxicology

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Much research interest has lately been focused on the dopamine transporter function in brain. Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods.

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Enhancement of in vivo binding of [123I]?-CIT by MK-801 in rat brain

Cited by 8 publications

References 53 publications

Positron Emission Tomography Studies of Potential Mechanisms Underlying Phencyclidine-Induced Alterations in Striatal Dopamine

Positron Emission Tomography Studies of Potential Mechanisms Underlying Phencyclidine-Induced Alterations in Striatal Dopamine

Imaging of striatal dopamine release elicited with NMDA antagonists: is there anything there to be seen?

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

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