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Titolo:
D3 dopamine receptor, behavioral sensitization, and psychosis
Autore:
Richtand, NM; Woods, SC; Berger, SP; Strakowski, SM;
Indirizzi:
Vet Adm Med Ctr, Dept Psychiat, Cincinnati, OH 45220 USA Vet Adm Med Ctr Cincinnati OH USA 45220 sychiat, Cincinnati, OH 45220 USA Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA Univ Cincinnati Cincinnati OH USA 45267 sychiat, Cincinnati, OH 45267 USA
Titolo Testata:
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
fascicolo: 5, volume: 25, anno: 2001,
pagine: 427 - 443
SICI:
0149-7634(200107)25:5<427:DDRBSA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENTRAL TEGMENTAL AREA; D-AMPHETAMINE CHALLENGE; INSITU HYBRIDIZATION HISTOCHEMISTRY; HUMAN COCAINE FATALITIES; EXCITATORY AMINO-ACIDS; RAT NUCLEUS-ACCUMBENS; IN-VIVO OCCUPANCY; WILD-TYPE MICE; D-3 RECEPTOR; LOCOMOTOR-ACTIVITY;
Keywords:
psychosis; behavioral sensitization; dopamine D3 receptor; schizophrenia; stimulant drugs; amphetamine; cocaine;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
200
Recensione:
Indirizzi per estratti:
Indirizzo: Richtand, NM Vet Adm Med Ctr, Dept Psychiat, V-116A,3200 Vine St, Cincinnati, OH 45220 USA Vet Adm Med Ctr V-116A,3200 Vine St Cincinnati OH USA 45220 A
Citazione:
N.M. Richtand et al., "D3 dopamine receptor, behavioral sensitization, and psychosis", NEUROSCI B, 25(5), 2001, pp. 427-443

Abstract

Behavioral sensitization is a progressive, enduring enhancement of behaviors that develops following repeated stimulant administration. It is mediated in part by dopaminergic pathways that also modulate a number of psychiatric conditions including the development of psychosis. We propose that down-regulation of D3 dopamine receptor function in critical brain regions contributes to sensitization. Rodent locomotion, a sensitizable behavior, is regulated by the opposing influence of dopamine receptor subtypes, with D3 stimulation opposing concurrent D1 and D2 receptor activation. The D3 dopaminereceptor has a 70-fold greater affinity for dopamine than D1 or D2 dopamine receptors. This imbalance in ligand affinity dictates greater occupancy for D3 than D1 or D2 receptors at typical dopamine concentrations following stimulant drug administration, resulting in differences in the relative tolerance at D3 vs D1 and D2 receptors. Sensitization may therefore result in part from accommodation of the inhibitory D3 receptor 'brake' on D1/D2 mediated behaviors, leading to a progressive locomotion increase following repeated stimulant exposure. The requirement for differential tolerance at D3 vs D1 and D2 receptors may explain the observed development of sensitizationfollowing application of cocaine, but not amphetamine, directly into nucleus accumbens. If correct, the 'D3 Dopamine Receptor Hypothesis' suggests D3antagonists could prevent sensitization, and may interrupt the developmentof psychosis when administered during the prodromal phase of psychotic illness. Additional study is needed to clarify the role of the D3 dopamine receptor in sensitization and psychosis. Published by Elsevier Science Ltd.

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Documento generato il 10/07/20 alle ore 09:46:22