title: Orexin-A increases cell surface expression of AMPA receptors in the striatum.
abstract: Accumulating evidence suggests that orexin signaling is involved in reward and motivation circuit functions. However, the underlying mechanisms are not yet fully understood. Here, we show that orexin-A potentiates AMPAR-mediated synaptic transmission in the striatum, possibly by regulating the surface expression of AMPARs. Primary culture of striatal neurons revealed increased surface expression of AMPARs following orexin-A treatment. The increase in surface-expressed AMPARs induced by orexin-A treatment was dependent on both ERK activation and the presence of extracellular Ca(2+). In the corticostriatal synapses of rat brain slices, orexin-A bath-application caused a delayed increase in the AMPAR/NMDAR EPSC ratio, suggesting that orexin-A sets in motion a series of events that lead to functional alterations in the striatal circuits. Our findings provide a potential link between the activation of orexin signaling in the striatum in response to addictive substances and neural adaptations in the reward circuitry that may mediate the long-lasting addiction-related behaviors.
authors.affiliation: School of Life sciences and Biotechnology, Korea University, Anam-dong 5-ga, Seongbuk-du, Seoul 136-701, Republic of Korea.
authors.forename: Hyun Sung
authors.initials: HS
authors.lastname: Shin
authors.forename: Hyeong Seok
authors.initials: HS
authors.lastname: Cho
authors.forename: Ki-Wug
authors.initials: KW
authors.lastname: Sung
authors.forename: Bong-June
authors.initials: BJ
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis*; D009435:Synaptic Transmission
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018091:Receptors, AMPA; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium