Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex.
Neuropharmacology
; 53(3): 369-78, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17631920
ABSTRACT
Prenatal exposure to the CB1 receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Delta9-tetrahydrocannabinol (Delta9-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in frontal cerebral cortex of adolescent offspring (40-day-old) with respect to those born from vehicle-treated mothers. WIN treatment induced a statistically significant enhancement of Vmaxl-[3H]glutamate uptake, whereas it did not modify glutamate Km, in frontal cerebral cortex synaptosomes of adolescent rats. Western blotting analysis, performed either in membrane proteins derived from homogenates and in proteins extracted from synaptosomes of frontal cerebral cortex, revealed that prenatal WIN exposure enhanced the expression of glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1). Moreover, immunocytochemical analyses of frontal cortex area revealed a more intense GLT1 and EAAC1 immunoreactivity (ir) distribution in the WIN-treated group. Collectively these results show that prenatal exposure to the cannabinoid CB1 receptor agonist WIN increases expression and functional activity of GLT1 and EAAC1 glutamate transporters (GluTs) associated to a decrease of cortical glutamate outflow, in adolescent rats. These findings may contribute to explain the mechanism underlying the cognitive impairment observed in the offspring of mothers who used marijuana during pregnancy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
/
Morfolinas
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Ácido Glutâmico
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Transportador 2 de Aminoácido Excitatório
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Benzoxazinas
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Transportador 3 de Aminoácido Excitatório
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Lobo Frontal
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Naftalenos
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Neuropharmacology
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Itália