Homer2 is necessary for EtOH-induced neuroplasticity.
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.
Szumlinski
Karen K
KK
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. szumlinski@psych.ucsb.edu
Lominac
Kevin D
KD
Oleson
Erik B
EB
Walker
Jennifer K
JK
Mason
Ashley
A
Dehoff
Marlin H
MH
Klugmann
Matthias
M
Klugman
Matthias
M
Cagle
Stephanie
S
Welt
Kristine
K
During
Matthew
M
Worley
Paul F
PF
Middaugh
Lawrence D
LD
Kalivas
Peter W
PW
D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D000072233:Homer Scaffolding Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012018:Reflex / Q000187:drug effects
D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D000072233:Homer Scaffolding Proteins; C000606625:Homer2 protein, mouse; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid