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Titolo:
5-HT3 RECEPTOR ACTIVATION IS REQUIRED FOR INDUCTION OF STRIATAL C-FOSAND PHOSPHORYLATION OF ATF-1 BY AMPHETAMINE
Autore:
GENOVA LM; HYMAN SE;
Indirizzi:
NINCDS,MOL PLAST SECT,NIH,BLDG 36,RM 4C-24,36 CONVENT DR BETHESDA MD 20892 HARVARD UNIV,PROGRAM NEUROSCI BOSTON MA 02115
Titolo Testata:
Synapse
fascicolo: 1, volume: 30, anno: 1998,
pagine: 71 - 78
SICI:
0887-4476(1998)30:1<71:5RAIRF>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT PROTEIN-KINASE; DOPAMINE RELEASE INVIVO; RAT NUCLEUS-ACCUMBENS; FREELY MOVING RATS; EXTRACELLULAR DOPAMINE; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; COCAINE; SEROTONIN; MICRODIALYSIS;
Keywords:
CYCLIC AMP RESPONSE ELEMENT BINDING PROTEIN; IMMEDIATE EARLY GENE; STRIATUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
L.M. Genova e S.E. Hyman, "5-HT3 RECEPTOR ACTIVATION IS REQUIRED FOR INDUCTION OF STRIATAL C-FOSAND PHOSPHORYLATION OF ATF-1 BY AMPHETAMINE", Synapse, 30(1), 1998, pp. 71-78

Abstract

Dopamine (DA) has been shown to be required for the induction of striatal gene expression by psychostimulants. However, direct DA agonists or selective inhibitors of DA reuptake are relatively weak inducers ofstriatal gene expression compared with cocaine or amphetamine. So although necessary, DA alone is not sufficient to mediate the full gene induction response to psychostimulants. In addition to its actions on the DA transporter, amphetamine also enhances serotonin (5-HT) release in the striatum. In this study, we investigated the mechanism by which5-HT contributes to the regulation of striatal gene expression by amphetamine. We found that selective lesions of serotonergic terminals inthe rat forebrain using 5,7-dihydroxytryptamine prevented the full induction of striatal c-Fos by 4 mg/kg amphetamine. Furthermore, amphetamine-induced striatal c-Fos was completely inhibited by administrationof the 5-HT3 receptor antagonist, MDL-72222, but not by the 5-HT2A/2Creceptor antagonist, ritanserin. Consistent with this finding, the induction of c-Fos by S-HT in primary cultures of E18 striatal neurons devoid of DA input was blocked by the 5-HT3 receptor antagonists, MDL-72222 and ICS 205-930, but not by 5-HT2A/2C antagonism. Additionally, blockade of 5-HT3 receptors by MDL-72222 inhibited the phosphorylation of activating transcription factor-1 (ATF-1) at Ser(63) by amphetamine, but not the phosphorylation of cAMP response element binding protein(CREB) at Ser(133). These results suggest that 5-HT3 receptor activation may be required for amphetamine-induced expression of ATF-l-regulated target genes in the striatum, which may include c-Fos. Synapse 30:71-78, 1998. (C) 1998 Wiley -Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 07:08:44