Effects of Milnacipran on Neuronal Excitability and Synaptic Transmission in Neurons of the Rat Locus Coeruleus

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  • ラット青斑核ニューロンの神経活動に対するｍｉｌｎａｃｉｐｒａｎの作用―ｍｅｔｈｙｌｐｈｅｎｉｄａｔｅとの比較―
  • methylphenidateとの比較

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Abstract

Effects of milnacipran (MIL), a selective serotonin and noradrenaline (NA) reuptake inhibitor, on the neuronal excitability and synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular and whole-cell patch-clamp recording techniques. We compared MIL and methylphenidate (MPH), a selective NA and dopamine reuptake inhibitor, as a therapeutic agent for attention deficit/hyperactivity disorder. Application of MPH (1-100μM) and MIL (1-100μM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response in LC neurons in a concentration-dependent manner. Spontaneous firing of LC neurons was blocked during the hyperpolarization. The MIL-induced hyperpolarization was blocked by yohimbine (1μM), an antagonist for α2- adrenoceptors. These results suggest that the MIL-induced hyperpolarization is mediated by NA via α2-adrenoceptors in LC neurons. Under the whole-cell patch-clamp condition, prolonged application of MIL produced an outward current which lasted as long as MIL existed in the ACSF. The outward current induced by NA was enhanced by MIL in LC neurons. MIL enhanced the amplitude and duration of the inhibitory postsynaptic potential, while it depressed the excitatory postsynaptic potential. The results indicated that both MIL and MPH showed almost the same effects on neuronal activity and synaptic transmission in the rat LC. These results suggest

Journal

  • NO TO HATATSU

    NO TO HATATSU 37 (1), 31-38, 2005

    THE JAPANESE SOCIETY OF CHILD NEUROLOGY

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