The role of hippocampal orexin-1 receptors (OX1R) in mediating the effect of morphine on CA1 baseline synaptic response and short term synaptic plasticity

Considering the increased activity of hypothalamic orexinergic neurons due to morphine administration, and its extensive projections to the hippocampus, it is probable that morphine effect on CA1 neuronal function is mediated by orexinergic system. So the effect of hippocampal orexin-1 receptors (OX1R) blockade on CA1 baseline synaptic response and short term synaptic plasticity was investigated. In this experimental study, animals received morphine 10 mg/kg/12h/(SC) for 10 days. SB-334867-A, OX1R antagonist (0.5μg/0.5 μl), was microinjected intrahippcampally for OX1R inhibition before each morphine injection. Baseline synaptic response and short term synaptic plasticity were evaluated by field potential recording. fEPSP was recorded from CA1 following Schaffer collaterals stimulation. After Input/Output construction, short term synaptic plasticity was induced by paired pulse stimulations. Chronic use of morphine did not affect the baseline synaptic response (p>0.05). SB- 334867-A microinjection in CA1 did not have any effect on baseline synaptic response in morphine dependent rats. Morphine increased paired pulse index (PPI) at 80 ms inter pulse interval (IPI, p<0.05). SB-334867-A pretreatment did not affect this morphine induced PPI change. The results suggest that orexin-1 receptors (OX1R) do not mediate the effect of morphine on baseline synaptic response and short term synaptic plasticity in CA1 area of the hippocampus.