Effect of long-term administration of the antidepressant drug milnacipran on serotonergic and noradrenergic neurotransmission in the rat hippocampus

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• 作者：Michel Weiss ; Pierre Blier ; Claude de Montigny
• 关键词：CA3 pyramidal cells ; Hippocampus ; Microiontophoresis ; Milnacipran ; NE and 5-HT transmission
• 刊名：Life Sciences
• 出版年：2007
• 出版时间：20 June 2007
• 年：2007
• 卷：81
• 期：2
• 页码：166-176
• 全文大小：1093 K

文摘

The effect of a long-term administration of the antidepressant milnacipran on the function of the serotonergic (5-HT) and noradrenergic (NE) systems was studied using single cell recording of CA3 hippocampal pyramidal cells in chloral hydrate-anesthetized male Sprague–Dawley rats, and in vitro [³H]5-HT release measurement from hippocampal slices. The sensitivity of neither the extrasynaptic nor that of the postsynaptic 5-HTb>1Ab> receptors of the pyramidal neurons was altered, as indicated by their unchanged responsiveness to the microiontophoretic application of 5-HT, and by the unchanged effect of the electrical stimulation at low frequency of the ascending 5-HT bundle, respectively. Increasing the frequency of stimulation (from 1 to 5 Hz) decreased its efficacy in control rats; the milnacipran treatment abolished this phenomenon. This cannot be attributed to a desensitisation of the terminal 5-HTb>1Bb> autoreceptor, since the suppressive effect of 5-HT agonist 5-carboxyamidotryptamine on [³H]5-HT release was enhanced in milnacipran-treated rats. As for the NE system, the unchanged suppressing effect of microiontophoretic applications of NE and that of the 5 Hz stimulation in the locus coeruleus (LC) on the firing activity of pyramidal neurons indicates that the milnacipran treatment not altered the sensitivity of extrasynaptic b1;b>2b>- and postsynaptic b1;b>1b>-adrenergic receptors on pyramidal cells, as well as that of the presynaptic b1;b>2b>-autoreceptor on NE terminals. The decreased inhibitory effect of NE on the [³H]5-HT release in milnacipran-treated rats revealed that this treatment results in a desensitisation of the presynaptic b1;b>2b>-heteroreceptor located on serotonergic terminals. Taken together with the decreased suppressive effect of a low frequency of stimulation of the NE tract, the present results suggest that long-term milnacipran treatment enhances the efficacy of the 5-HT and reduces that of the NE neurotransmission.