Low neuropeptide Y (NPY) and cAMP-dependent protein kinase A (PKA) signaling are both associated with increased ethanol consumption and enhanced sensitivity to ethanol-induced locomotor stimulation. Recent evidence shows that PKA signaling drives NPY synthesis. Therefore, the guiding hypothesis of the present proposal is that the increased ethanol intake and sensitivity to ethanol-induced locomotor sensitization that are characteristic of mutant mice with low central PKA activity (i.e., Rll-beta deficient mice) are consequences of blunted NPY signaling.
Specific Aim 1 will utilize immunohistochemistry and real-time PCR to determine if PKA mutant mice have low NPY signaling at baseline and in response to ethanol administration in candidate brain regions.
Specific Aim 2 will utilize a recombinant adeno-associated viral vector (rAAV) to determine if site-directed overexpressioh of NPY in the striatum, nucleus accumbens, and/or amygdala will protect against increased sensitivity to ethanol-induced locomotor sensitization and elevated ethanol drinking in PKA mutant mice. These studies will provide important insight into the interactions between PKA and NPY signaling in modulating neurobiological responses to ethanol.
| Hayes, Dayna M; Fee, Jon R; McCown, Thomas J et al. (2012) Neuropeptide Y signaling modulates the expression of ethanol-induced behavioral sensitization in mice. Addict Biol 17:338-50 |
