title: Neuropeptide Y signaling modulates the expression of ethanol-induced behavioral sensitization in mice.
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.
authors.affiliation: Department of Psychology, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Dayna M
authors.initials: DM
authors.lastname: Hayes
authors.forename: Jon R
authors.initials: JR
authors.lastname: Fee
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McCown
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Knapp
authors.forename: George R
authors.initials: GR
authors.lastname: Breese
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cubero
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Lerma-Cabrera
authors.forename: Montserrat
authors.initials: M
authors.lastname: Navarro
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C062924:neuropeptide Y (13-36); C095889:neuropeptide Y2 receptor; D000431:Ethanol; D017868:Cyclic AMP-Dependent Protein Kinases