Abstract
The nucleus locus coeruleus (LC) contains cell bodies of noradrenergic neurons and has widespread projection of noradrenergic neurons to cerebrum, thalamus, limbic system, hypothalamus, brain stem and spinal cord. Milnacipran is a recently released antidepressant as a class of a selective serotonin and noradrenaline re-uptake inhibitor (SNRI). In this study, we examined the effect of milnacipran on activity of LC neurons by using an intracellular recording and a whole-cell patch clamp technique. Bath application of milnacipran (0.3-100 μM) produced a hyperpolarizing response in LC neurons. Yohimbine, α2 receptor antagonist, inhibited milnacipran induced hyperpolarization. Milnacipran (0.3-10 μM) increased the amplitude and the time course of the inhibitory postsynaptic current (IPSC) mediated by NA in LC neurons. Milnacipran (3-10 μM) significantly inhibited the amplitude of an excitatory postsynaptic current (EPSC) and such an inhibitory effect on EPSCs was attenuated by WAY100635, an 5-HT1A receptor antagonist. We discuss the effects of milnacipran on membrane potential and synaptic transmission on LC neurons and compare milnacipran with methylphenidate that is the most common therapeutic agent to improve major symptoms of attention deficit/hyperactivity disorder (AD/HD). [Jpn J Physiol 54 Suppl:S150 (2004)]
