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Titolo:
EFFECT OF DOPAMINERGIC DRUGS ON THE IN-VIVO BINDING OF [H-3] WIN-35,428 TO CENTRAL DOPAMINE TRANSPORTERS
Autore:
SCHEFFEL U; STEINERT C; KIM SE; EHLERS MD; BOJA JW; KUHAR MJ;
Indirizzi:
JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED BALTIMORE MD 21205 JOHNS HOPKINS MED INST,DEPT NEUROSCI BALTIMORE MD 21205 NIDA,ADDICT RES CTR,NEUROSCI BRANCH BALTIMORE MD 21224
Titolo Testata:
Synapse
fascicolo: 2, volume: 23, anno: 1996,
pagine: 61 - 69
SICI:
0887-4476(1996)23:2<61:EODDOT>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; F-18 GBR 13119; COCAINE RECOGNITION SITES; INVIVO MICRODIALYSIS; RAT STRIATUM; KINETIC-PROPERTIES; PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; UPTAKE INHIBITOR; REUPTAKE SITES;
Keywords:
IN VIVO BINDING; DA TRANSPORTER; [H-3] WIN35,428; L-DOPA; D-AMPHETAMINE; ALPHA-METHYL-DL-P-TYROSINE; GAMMA-BUTYROLACTONE; L-DEPRENYL; HALOPERIDOL; APOMORPHINE; BROMOCRIPTINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
72
Recensione:
Indirizzi per estratti:
Citazione:
U. Scheffel et al., "EFFECT OF DOPAMINERGIC DRUGS ON THE IN-VIVO BINDING OF [H-3] WIN-35,428 TO CENTRAL DOPAMINE TRANSPORTERS", Synapse, 23(2), 1996, pp. 61-69

Abstract

[C-11]WIN 35,428 (also designated [C-11]CFT) is now being used in several positron emission tomography (PET) centers to image dopamine (DA)transporter sites in the mammalian brain. Whether and to what extent in vivo WIN 35,428 binding is influenced by intra- and extrasynaptic dopamine levels are largely unknown. The purpose of the present study was to evaluate the effects of various drugs, known to affect DA levelsand release, on the binding of [H-3]WIN 35,428 to central DA transporters in the mouse brain. D-Amphetamine, which releases DA from neuronsand blocks the DA transporter directly, inhibited striatal [H-3]WIN 35,428 binding in dose-dependent manner. Similarly, alpha-methyl-DL-p-tyrosine, an inhibitor of tyrosine hydroxylase, blocked [H-3]WIN 35,428binding, possibly via competitive inhibition by the metabolite p-hydroxyamphetamine. Specific binding of [H-3]WIN 35,428 was insensitive tochanges in synaptic DA levels caused by pretreatment of the animals with high doses of D-2 receptor agonists (apomorphine, bromocriptine), antagonists (haloperidol) or the inhibitor of dopaminergic neuron firing gamma-butyrolactone (GEL). High doses (> 50 mg/kg) of L-DOPA (in combination with benserazide), however, reduced [H-3]WIN 35,428 binding significantly, yet for a relatively short time (approximately 2.5 h). Chronic treatment with L-deprenyl elicited no changes in in vivo [H-3]WIN 35,428 accumulation in the striatum. Neurotoxic damage of DA neurons caused by administration of high doses of amphetamine was detected in the striatum by a significant reduction in [H-3]WIN 35,428 binding 7 days after cessation of amphetamine treatment. Thus, [H-3]WIN 35,428binding was only affected by neurotoxic loss of neurons, by administration of uptake inhibitors, or by some treatments which significantly elevate DA levels. Compounds which inhibit DA release or deplete DA acutely do not increase [H-3]WIN 35,428 binding, suggesting that normal or ''resting'' levels of DA are not sufficient to alter [H-3]WIN 35,428 binding in vivo. These findings are important for our understanding of the function and regulation of the DA transporter, as well as the in vivo binding of the radioligand [H-3/C-11]WIN 35,428. Moreover, theywill be important for the interpretation of PET studies in which [C-11]WIN 35,428 is used to assess the integrity of dopaminergic neurons. (C) 1996 Wiley-Liss, Inc.

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Documento generato il 23/01/21 alle ore 09:57:14