Effects of milnacipran on the inhibitory postsynaptic potential in neurons of the rat locus coeruleus

Effects of milnacipran (MIL), a serotonin and noradrenaline reuptake inhibitor (SNRI), on synaptic transmission were examined in the rat locus coeruleus (LC). Bath-application of MIL produced a hyperpolarization associated with a decrease in input resistance of LC neurons. The MIL-induced hyperpolarization reversed polarity near the equilibrium potential of K+. The MIL-induced hyperpolarization was blocked by yohimbine (1 microM). Clonidine, but not serotonin (5-hydroxytryptamine; 5-HT), produced a hyperpolarizing potential in LC neurons. The MIL-induced hyperpolarization reversed polarity at -114 +/- 3 mV (n=4). MIL (0.1-10 microM) depressed the amplitude of the excitatory postsynaptic potential (EPSP), while it enhanced the amplitude and duration of the inhibitory postsynaptic potential (IPSP). These results suggest that MIL hyperpolarizes LC neurons and enhances the IPSP by increasing endogenous noradrenaline (NA) concentration at synapses in LC neurons.