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Neuropeptide Y signaling modulates the expression of ethanol‐induced behavioral sensitization in mice
Author(s) -
Hayes Dayna M.,
Fee Jon R.,
McCown Thomas J.,
Knapp Darin J.,
Breese George R.,
Cubero Inmaculada,
Carvajal Francisca,
LermaCabrera Jose Manuel,
Navarro Montserrat,
Thiele Todd E.
Publication year - 2012
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2011.00336.x
Subject(s) - sensitization , neuropeptide y receptor , nucleus accumbens , striatum , neuropeptide , endocrinology , medicine , receptor , agonist , medium spiny neuron , chemistry , biology , neuroscience , dopamine
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.