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Titolo:
Sensitivity of binding of high-affinity dopamine receptor radioligands to increased synaptic dopamine
Autore:
Gatley, SJ; Gifford, AN; Carroll, FI; Volkow, ND;
Indirizzi:
Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA Brookhaven Natl Lab Upton NY USA 11973 Lab, Dept Med, Upton, NY 11973 USA Res Triangle Inst, Res Triangle Pk, NC 27709 USA Res Triangle Inst Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA
Titolo Testata:
SYNAPSE
fascicolo: 4, volume: 38, anno: 2000,
pagine: 483 - 488
SICI:
0887-4476(200012)38:4<483:SOBOHD>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOGENOUS DOPAMINE; BEHAVIORAL SENSITIZATION; NONHUMAN-PRIMATES; I-125 EPIDEPRIDE; C-11 RACLOPRIDE; RAT-BRAIN; COCAINE; INVIVO; AMPHETAMINE; RELEASE;
Keywords:
dopamine; dopamine transporter; positron emission tomography; epidepride; SCH 23390;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Gatley, SJ Brookhaven Natl Lab, Dept Med, 490 Bell Ave, Upton, NY 11973 USA Brookhaven Natl Lab 490 Bell Ave Upton NY USA 11973 Y 11973 USA
Citazione:
S.J. Gatley et al., "Sensitivity of binding of high-affinity dopamine receptor radioligands to increased synaptic dopamine", SYNAPSE, 38(4), 2000, pp. 483-488

Abstract

PET and SPECT studies have documented that D2 radioligands of moderate affinity? but not radioligands of high affinity, are sensitive to pharmacological challenges that alter synaptic dopamine levels. The objective of this work was to determine whether the brain kinetics of high-affinity radioligands for dopamine D1 ([H-3]SCH 23390) and D2 ([I-123]epidepride) receptors were altered by a prolonged elevation of synaptic dopamine induced by the potent cocaine analog RTI-55. Mice were injected intravenously with radioligands either 30 min after or 4 h before intraperitoneal administration of RTI-55 (2 mg/kg). In separate experiments, the pharmacological effects of RTI-55 were assessed biochemically by measuring uptake of dopamine in synaptosomes prepared from RTI-treated mice and behaviorally by monitoring locomotor activity. Consistent with the expected elevation of synaptic dopamine, RTI-55 induced a long-lasting decrement in dopamine uptake measured ex vivo, and a prolonged increase in locomotor activity. RTI-55 injected prior to the radioligands induced a significant(P < 0.05) increase in striatal concentration of [I-123]epidepride at 15 min, relative to saline-treated controls, but there were no differences between the two groups at later time-points. For [H-3]SCH 23390, both initial striatal uptake and subsequent clearance were slightly increased by preadministration of RTI-55. Administration of RTI-55 4 h after the radioligands (i.e., when it was presumed that a state of near equilibrium binding of the radioligands had been reached), was associated with a significant reduction of striatal radioactivity for both radiotracers. Our results are consistent with increased competition between dopamine and radioligand for binding to both D1 and D2 receptors after treatment with RTI-55. We suggest that the magnitude of the competition is reduced byfailure of the receptor binding of high-affinity radioligands to rapidly attain equilibrium. (C) 2000 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/11/19 alle ore 03:01:58