Orexin receptors mediate long-term depression of excitatory synaptic transmission in the spinal cord dorsal horn.

Abstract:

:Neuropeptides orexin-A and -B are related to the regulation of sleep/wakefulness and feeding behaviors. Recently, the peptides have also been shown to yield antinociceptive effects in various pain models. However, it is not clear whether orexins are involved in forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), the increase and the decrease of synaptic efficacy, respectively. In the present study, we examined whether orexin receptor type 1 (OX1) and 2 (OX2) are involved in the induction or maintenance of LTD of excitatory synaptic transmission using transverse spinal cord slices of young rats. Repetitive electrical stimulation of Lissauer's tract zone at 2Hz for 5min (600 pulses), combined with a holding potential of -30mV, induced LTD of the amplitude of excitatory postsynaptic currents (EPSCs) which are evoked by the activation of primary afferent fibers. The maintenance of LTD was significantly prevented by bath application of SB674042 (1μM), an OX1 antagonist, or EMPA (1μM), an OX2 antagonist. In addition, LTD was dependent on the NMDA receptor, as the NMDA receptor antagonist D-AP5 blocked the maintenance of LTD. Our study suggests that orexins, via activation of both OX1 and OX2, play a significant role in the expression of NMDA-dependent LTD, thereby contributing to the spinal modulation of pain transmission.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Park KB,Weon H

doi

10.1016/j.neulet.2017.08.068

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

12-16

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(17)30728-0

journal_volume

660

pub_type

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