Neuropeptide Y signaling modulates the expression of ethanol-induced behavioral sensitization in mice.
Addict Biol
; 17(2): 338-50, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-21762289
ABSTRACT
Neuropeptide Y (NPY) and protein kinase A (PKA) have been implicated in neurobiological responses to ethanol. We have previously reported that mutant mice lacking normal production of the RIIß subunit of PKA (RIIß-/- mice) show enhanced sensitivity to the locomotor stimulant effects of ethanol and increased behavioral sensitization relative to littermate wild-type RIIß+/+ mice. We now report that RIIß-/- mice also show increased NPY immunoreactivity in the nucleus accumbens (NAc) core and the ventral striatum relative to RIIß+/+ mice. These observations suggest that elevated NPY signaling in the NAc and/or striatum may contribute to the increased sensitivity to ethanol-induced behavioral sensitization that is a characteristic of RIIß-/- mice. Consistently, NPY-/- mice failed to display ethanol-induced behavioral sensitization that was evident in littermate NPY+/+ mice. To examine more directly the role of NPY in the locomotor stimulant effects of ethanol, we infused a recombinant adeno-associated virus (rAAV) into the region of the NAc core of DBA/2J mice. The rAAV-fibronectin (FIB)-NPY(13-36) vector expresses and constitutively secretes the NPY fragment NPY(13-36) (a selective Y(2) receptor agonist) from infected cells in vivo. Mice treated with the rAAV-FIB-NPY(13-36) vector exhibited reduced expression of ethanol-induced behavioral sensitization compared with mice treated with a control vector. Taken together, the current data provide the first evidence that NPY signaling in the NAc core and the Y(2) receptor modulate ethanol-induced behavioral sensitization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gânglios da Base
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Neuropeptídeo Y
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Depressores do Sistema Nervoso Central
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Proteínas Quinases Dependentes de AMP Cíclico
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Etanol
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Núcleo Accumbens
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article