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Published on: May 25, 2011
Orexin A presynaptically decreases inhibitory synaptic transmission in rat locus coeruleus neurons
Hossein Mohammad-Pour Kargar1, Hossein Azizi2, Javad Mirnajafi-Zadeh2
1Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Biology, Faculty of Sciences, Islamjc Azad University, Damghan branch, Damghan, Iran.
Abstract:
Locus coeruleus nucleus (LC) is a major noradrenergic nucleus in the brain. It receives dense orexinergic projections from lateral hypothalamus. Whilst it is known that orexin A increases firing rate of LC neurons, its effect on spontaneous and evoked inhibitory postsynaptic currents (sIPSCs and eIPSCs, respectively) has not been yet identified. In this research, we investigated the effect of orexin A on eIPSCs and sIPSCs in LC neurons. Whole-cell recordings revealed that orexin A suppresses eIPSCs amplitude in which this effect was blocked by an orexin type-1 receptors antagonist (SB-334867) and cannabinoid type-1 (CB1) receptors antagonist (AM251). Moreover, exposure of neurons to BAPTA (Ca2+ chelator) and U73122 (phospholipase C inhibitor) prevented orexin A-induced eIPSCs depression. On the other hand, orexin A increased pair pulse ratio and sIPSCs frequency but had no effect on sIPSCs amplitude. Our results revealed that eIPSCs suppression in the LC is mediated by CB1 receptor through a presynaptic mechanism.
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