Regulation of central synaptic transmission by 5-HT1B auto- and heteroreceptors
Regulation of central synaptic transmission by 5-HT1B auto- and heteroreceptors
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DOI：
10.1124/mol.58.6.1271
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发表时间：
2000-12-01
影响因子：
3.6
通讯作者：
Williams, JT
中科院分区：
文献类型：
--
作者：
Morikawa, H;Manzoni, OJ;Williams, JT
尽管5-HT 1B受体被认为在神经末梢上表达，但由于缺乏选择性拮抗剂，它们的确切作用方式尚未完全了解。在本研究中使用5-HT 1B受体敲除小鼠来评估5-HT 1B受体在中枢神经系统的三个区域（中缝背侧、中脑腹侧和延髓核）的突触传递的调制中的功能。N-（3-三氟甲基苯基）哌嗪，5-HT 1B受体激动剂，有效地抑制5-HT 1A受体介导的慢抑制性突触后电位（IPSPs）在野生型，但不是敲除小鼠中缝背核。突触释放的5-HT和外源性5-HT引起的突触前抑制，持续超过突触后超极化只有在野生型小鼠。在中脑腹侧，多巴胺神经元中γ-氨基丁酸（B）IPSP的5-HT 1 B受体依赖性抑制存在于野生型动物中，而在敲除动物中不存在。在测量中型多刺神经元中谷氨酸介导的兴奋性突触后电流的延髓核中获得了类似的结果。最后，可卡因，它阻止5-HT的摄取，抑制IPSPs在中缝背侧和腹侧中脑的野生型，但不敲除小鼠，而可卡因产生类似的抑制兴奋性突触后电流在两种类型的动物的丘脑核。这些结果表明，5-HT 1B受体作为自身受体和异源受体发挥作用，在中枢神经系统中对递质释放产生突触前抑制。此外，这项研究强调了突触前5-HT 1B受体在介导可卡因对突触传递的影响中所起的作用。
Although 5-HT1B receptors are believed to be expressed on nerve terminals, their precise mode of action is not fully understood because of the lack of selective antagonists. The 5-HT1B receptor knockout mouse was used in the present investigation to assess the function of 5-HT1B receptors in the modulation of synaptic transmission in three areas of the central nervous system: the dorsal raphe, the ventral midbrain, and the nucleus accumbens. N-(3-Trifluoromethylphenyl) piperazine, a 5-HT1B receptor agonist, potently inhibited 5-HT1A receptor-mediated slow inhibitory postsynaptic potentials (IPSPs) in the dorsal raphe of wild-type but not knockout mice. Both synaptically released 5-HT and exogenous 5-HT caused a presynaptic inhibition that outlasted the postsynaptic hyperpolarization only in wild-type mice. In the ventral midbrain, 5-HT1B receptor-dependent inhibition of gamma -aminobutyric acid(B) IPSPs in dopamine neurons was present in wildtype animals and absent in knockout animals. Similar results were obtained in the nucleus accumbens measuring glutamate-mediated excitatory postsynaptic currents in medium spiny neurons. Finally, cocaine, which blocks 5-HT uptake, inhibited IPSPs in the dorsal raphe and the ventral midbrain of wild-type but not knockout mice, whereas cocaine produced comparable inhibition of excitatory postsynaptic currents in the nucleus accumbens of both types of animals. These results indicate that 5-HT1B receptors function as autoreceptors and heteroreceptors to exert presynaptic inhibition of transmitter release in the central nervous system. Furthermore, this study underscores the role played by presynaptic 5-HT1B receptors in mediating the effects of cocaine on synaptic transmission.