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- Title
Neuropeptide Y signaling modulates the expression of ethanol-induced behavioral sensitization in mice.
- Authors
Hayes, Dayna M; Fee, Jon R; McCown, Thomas J; Knapp, Darin J; Breese, George R; Cubero, Inmaculada; Carvajal, Francisca; Lerma-Cabrera, Jose Manuel; Navarro, Montserrat; Thiele, Todd E
- 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 RIIβ subunit of PKA (RIIβ-/- mice) show enhanced sensitivity to the locomotor stimulant effects of ethanol and increased behavioral sensitization relative to littermate wild-type RIIβ+/+ mice. We now report that RIIβ-/- mice also show increased NPY immunoreactivity in the nucleus accumbens (NAc) core and the ventral striatum relative to RIIβ+/+ 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 RIIβ-/- 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.
- Publication
Addiction biology, 2012, Vol 17, Issue 2, p338
- ISSN
1369-1600
- Publication type
Journal Article
- DOI
10.1111/j.1369-1600.2011.00336.x