RT Journal Article
SR Electronic
T1 Homer2 Is Necessary for EtOH-Induced Neuroplasticity
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7054
OP 7061
DO 10.1523/JNEUROSCI.1529-05.2005
VO 25
IS 30
A1 Szumlinski, Karen K.
A1 Lominac, Kevin D.
A1 Oleson, Erik B.
A1 Walker, Jennifer K.
A1 Mason, Ashley
A1 Dehoff, Marlin H.
A1 Klugman, Matthias
A1 Cagle, Stephanie
A1 Welt, Kristine
A1 During, Matthew
A1 Worley, Paul F.
A1 Middaugh, Lawrence D.
A1 Kalivas, Peter W.
YR 2005
UL http://www.jneurosci.org/content/25/30/7054.abstract
AB Homer proteins are integral to the assembly of proteins regulating glutamate signaling and synaptic plasticity. Constitutive Homer2 gene deletion [knock-out (KO)] and rescue with adeno-associated viral (AAV) transfection of Homer2b was used to demonstrate the importance of Homer proteins in neuroplasticity produced by repeated ethanol (EtOH) administration. Homer2 KO mice avoided drinking high concentrations of EtOH and did not develop place preference or locomotor sensitization after repeated EtOH administration. The deficient behavioral plasticity to EtOH after Homer2 deletion was paralleled by a lack of augmentation in the rise in extracellular dopamine and glutamate elicited by repeated EtOH injections. The genotypic differences in EtOH-induced change in behavior and neurochemistry were essentially reversed by AAV-mediated transfection of Homer2b into accumbens cells including, differences in EtOH preference, locomotor sensitization, and EtOH-induced elevations in extracellular glutamate and dopamine. These data demonstrate a necessary and active role for accumbens Homer2 expression in regulating EtOH-induced behavioral and cellular neuroplasticity.