Selective serotonin reuptake inhibitors reduce the spontaneous activity of dopaminergic neurons in the ventral tegmental area
Selective serotonin reuptake inhibitors reduce the spontaneous activity of dopaminergic neurons in the ventral tegmental area
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DOI：
10.1016/s0361-9230(98)00054-9
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发表时间：
1998-08-01
影响因子：
3.8
通讯作者：
Esposito, E
中科院分区：
文献类型：
--
作者：
Di Mascio, M;Di Giovanni, G;Esposito, E
采用电生理技术研究帕罗西汀、舍曲林和氟伏沙明对大鼠腹侧被盖区（VTA）多巴胺能神经元基础活性的影响。急性静脉注射帕罗西汀（20-1280 μ g/kg）、舍曲林（20-1280 μ g/kg）和氟伏沙明（20-1280 μ g/kg）可引起所研究的VTA多巴胺能细胞的放电率轻微但显著降低。帕罗西汀在累积剂量为160 μ g/kg时，最大抑制作用为10 +/- 11%。舍曲林对VTA多巴胺能神经元有剂量相关的抑制作用，在累积剂量为1280 μ g/kg时达到最大（10 +/- 7%）。与帕罗西汀和舍曲林相比，氟伏沙明对VTA多巴胺能神经元基础放电率的影响更为明显，在累积剂量为1280 μ g/kg时，其最大抑制率为17 +/- 12%。急性静脉注射帕罗西汀（20 ~ 1280 μ g/kg）、舍曲林（20 ~ 1280 μ g/kg）和氟伏沙明（20 ~ 5120 μ g/kg）均可引起中脑背核5 -羟色胺能神经元基础放电速率呈剂量依赖性降低，累计剂量为1280 μ g/kg时，帕罗西汀和舍曲林可阻止5 -羟色胺能神经元的自发放电，而氟伏沙明仅在累计剂量为5120 μ g/kg时才有相同效果。5-HT1A受体拮抗剂特他洛尔（1mg /kg，静脉注射）预处理降低了帕罗西汀、氟伏沙明和舍曲林对DRN中5-羟色胺能神经元基础活性的抑制作用，特他洛尔诱导氟伏沙明的ED50增加15倍。对帕罗西汀和舍曲林对5 -羟色胺能神经元活性的抑制作用，特他洛尔的拮抗作用不明显，但对VTA多巴胺能神经元基础活性的抑制作用，特他洛尔预处理（1 mg/kg，静脉滴注）增强。特他洛尔不影响帕罗西汀和舍曲林对这些神经元的抑制作用。综上所述，抑制VTA多巴胺能神经元的基础放电速率是选择性血清素再摄取抑制剂（SSRIs）的共同特征。SSRIs对VTA多巴胺能细胞活性的影响可能与其治疗作用有关，并可能解释报道的静坐症病例的起源，(C) 1998 Elsevier Science Inc.。
Electrophysiological techniques were used to study the effects of paroxetine, sertraline, and fluvoxamine on the basal activity of dopaminergic neurons in the ventral tegmental area (VTA) of rats. Acute i.v. administrations of paroxetine (20-1280 mu g/kg), sertraline (20-1280 mu g/kg), and fluvoxamine (20-1280 mu g/kg) caused a slight but significant reduction in the firing rate of the VTA dopaminergic cells studied. Paroxetine produced a maximal inhibitory effect of 10 +/- 11% at the cumulative dose of 160 mu g/kg. Sertraline induced a dose-related inhibition of VTA dopaminergic neurons, which reached its maximum (10 +/- 7%) at the cumulative dose of 1280 mu g/kg. The effect of fluvoxamine on the basal firing rate of VTA dopaminergic neurons was more pronounced as compared to that of paroxetine and sertraline, in that it produced a maximal inhibition of 17 +/- 12% at the cumulative dose of 1280 mu g/kg. Acute i.v. injections of paroxetine (20-1280 mu g/kg), sertraline (20-1280 mu g/kg), and fluvoxamine (20-5120 mu g/kg) caused a dose-dependent decrease in the basal firing rate of serotonergic neurons in the dorsal raphe nucleus (DRN), Paroxetine and sertraline stopped the spontaneous firing of serotonergic neurons at the cumulative dose of 1280 mu g/kg, whereas fluvoxamine reached the same effect only at the cumulative dose of 5120 mu g/kg, Pretreatment with the 5-HT1A receptor antagonist tertatolol (1 mg/kg, i.v.) reduced the inhibitory effects of paroxetine, fluvoxamine, and sertraline on the basal activity of serotonergic neurons in the DRN, Administration of tertatolol induced a 15-fold increase in the ED50 for fluvoxamine. The antagonistic effect of tertatolol was much less evident in blocking the inhibitory action exerted by paroxetine and sertraline on the activity of serotonergic neurons, Pretreatment with tertatolol (1 mg/kg, i.v.) potentiated the inhibitory effect of fluvoxamine on the basal activity of VTA dopaminergic neurons. Tertatolol did not affect the inhibitory action exerted by paroxetine and sertraline on these neurons. It is concluded that inhibition of the basal firing rate of dopaminergic neurons in the VTA is a common characteristic of selective serotonin reuptake inhibitors (SSRIs). The effects of SSRIs on VTA dopaminergic cell activity might be relevant for their therapeutic action and may explain the origin of the reported cases of akathisia, (C) 1998 Elsevier Science Inc.