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Titolo:
The potent, selective mGlu2/3 receptor agonist LY379268 increases extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole-3-acetic acid in the medial prefrontal cortex of the freely moving rat
Autore:
Cartmell, J; Perry, KW; Salhoff, CR; Monn, JA; Schoepp, DD;
Indirizzi:
Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Neurosci Res, Indianapolis, IN 46285 USA Eli Lilly & Co Indianapolis IN USA 46285 Res, Indianapolis, IN 46285 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 3, volume: 75, anno: 2000,
pagine: 1147 - 1154
SICI:
0022-3042(200009)75:3<1147:TPSMRA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
METABOTROPIC GLUTAMATE RECEPTORS; INDUCED STEREOTYPED BEHAVIORS; PHARMACOLOGICAL CHARACTERIZATION; ANTIPSYCHOTIC DRUG; NUCLEUS-ACCUMBENS; IN-VIVO; METABOLISM; STRIATUM; RELEASE; BRAIN;
Keywords:
metabotropic glutamate receptor; microdialysis; clozapine; LY379268;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Schoepp, DD Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Neurosci Res, Drop 0510, Indianapolis, IN 46285 USA Eli Lilly & Co Drop 0510 IndianapolisIN USA 46285 N 46285 USA
Citazione:
J. Cartmell et al., "The potent, selective mGlu2/3 receptor agonist LY379268 increases extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole-3-acetic acid in the medial prefrontal cortex of the freely moving rat", J NEUROCHEM, 75(3), 2000, pp. 1147-1154

Abstract

Previous work has shown that the potent, selective metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the atypical antipsychotic clozapine in behavioral assays. To investigate further the potential antipsychotic actions of this agent, we examined the effects of LY379268 using microdialysis in awake, freely moving rats, on extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) in rat medial prefrontal cortex, Systemic LY379268 increased extracellular levels of dopamine, DOPAC, HVA, and 5-HIAAin a dose-dependent, somewhat delayed manner, LY379268 (3 mg/kg s.c.) increased levels of dopamine, DOPAC, HVA, and 5-HIAA to 168, 170, 169, and 151%of basal, respectively. Clozapine (10 mg/kg) also increased dopamine, DOPAC, and HVA levels, with increases of 255, 262, and 173%, respectively, but was without effect on extracellular 5-HIAA levels. The increases in DOPAC, HVA, and 5-HIAA levels by 3 mg/kg LY379268 were reversed by the selective mGlu2/3 receptor antagonist LY341495 (1 mg/kg), Furthermore, LY379268 (3 mg/kg)-evoked increases in DOPAC and HVA were partially blocked and the increase in 5-HIAA was completely blocked by local application of 3 mu M tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists activate dopaminergic and serotonergic brain pathways previously associated with the action of atypical antipsychotics such as clozapine and other psychiatric agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 07:28:58