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Titolo:
A comparison of the acute effects of zotepine and other antipsychotics on rat cortical dopamine release, in vivo
Autore:
Rowley, HL; Needham, PL; Kilpatrick, IC; Heal, DJ;
Indirizzi:
BASF Pharma Res & Dev, Nottingham NG1 1GF, England BASF Pharma Res & Dev Nottingham England NG1 1GF ingham NG1 1GF, England
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 2, volume: 361, anno: 2000,
pagine: 187 - 192
SICI:
0028-1298(200002)361:2<187:ACOTAE>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
FREELY MOVING RATS; MEDIAL PREFRONTAL CORTEX; DOUBLE-BLIND TRIAL; PATIENTS RECEIVING CLOZAPINE; SCHIZOPHRENIC-PATIENTS; NUCLEUS-ACCUMBENS; NEGATIVE SYMPTOMS; FRONTAL-CORTEX; IN-VIVO; EXTRACELLULAR DOPAMINE;
Keywords:
zotepine; dopamine; microdialysis; frontal cortex; atypical antipsychotics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Rowley, HL BASF Pharma Res & Dev, Pennyfoot St, Nottingham NG1 1GF, England BASF Pharma Res & Dev Pennyfoot St Nottingham England NG1 1GF
Citazione:
H.L. Rowley et al., "A comparison of the acute effects of zotepine and other antipsychotics on rat cortical dopamine release, in vivo", N-S ARCH PH, 361(2), 2000, pp. 187-192

Abstract

The acute effects of systemic administration of the antipsychotic drug, zotepine, on extracellular dopamine (DA) in the frontal cortex of freely-moving rats were stud led using in vivo microdialysis and compared with the actions of clozapine, olanzapine and haloperidol. Treatment with zotepine (1.0 mg/kg, i.p.) resulted in a prolonged elevation of cortical DA levels for up to 180 min post-drug. A maximal rise of +333% was observed at 120 min post-zotepine treatment. Clozapine (10.0 mg/kg, i.p.) also evoked a rise in extracellular DA which was similar in duration (200 min) to that resulting from treatment with zotepine. A maximal rise of 223% was observed at 100 min post-clozapine treatment. Olanzapine (1.0 mg/kg, i.p.) resulted in an immediate increase in DA levels which was maximal 40 min post-treatment (+280%) with levels returning to pre-injection valuesby 100 min after dosing. In contrast, haloperidol (0.1 mg/kg, i.p.) had nomeasurable influence on cortical DA levels. Local perfusion with the NA uptake inhibitor, nisoxetine (10 mu M), resulted in an increase in cortical DA levels which was maximal alt 100 min post-onset of perfusion (+257% abovebaseline). Administration of zotepine (1.0 mg/kg, i.p.) during nisoxetine perfusion elevated DA levels to a maximum of +301% above baseline, 60 min post-zotepine. These results show that acute administration of each of three drugs with an atypical antipsychotic profile causes an elevation of cortical DA in freely-moving rats at doses relevant to those derived from animal models which predict antipsychotic activity. As a dysfunction in cortical DA is thought to be involved in both the negative symptoms of schizophrenia and cognitivedeficits in schizophrenic patients, it is possible that zotepine's abilityto elevate cortical DA levels may underlie its effectiveness in successfully treating these components of schizophrenia. Furthermore, the ability of zotepine to elevate cortical DA is more likely to derive from its inhibition of the NA transporter rather than DA receptor blockade in this region.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 21:06:30