Orexin-A increases cell surface expression of AMPA receptors in the striatum |
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Authors: | Hyun Sung Shin Ki-Wug Sung |
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Institution: | a School of Life sciences and Biotechnology, Korea University, Anam-dong 5-ga, Seongbuk-du, Seoul 136-701, Republic of Korea b Department of Pharmacology, Medical Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea |
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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 Ca2+. 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. |
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Keywords: | Orexin-A AMPA receptor Synaptic plasticity Drug addiction |
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