Varenicline and nicotine enhance GABAergic synaptic transmission in rat CA1 hippocampal and medial septum/diagonal band neurons.
Varenicline and nicotine enhance GABAergic synaptic transmission in rat CA1 hippocampal and medial septum/diagonal band neurons.
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DOI：
10.1016/j.lfs.2012.12.013
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发表时间：
2013-03-14
期刊：
影响因子：
6.1
通讯作者：
Winzer-Serhan, Ursula H.
中科院分区：
文献类型：
--
作者：
DuBois, Dustin W.;Damborsky, Joanne C.;Fincher, Annette S.;Frye, Gerald D.;Winzer-Serhan, Ursula H.
FDA批准的戒烟辅助药物伐尼克兰可以有效地减弱尼古丁刺激的多巴胺释放。伐尼克兰还可能对其他递质系统产生重要作用，这些递质系统也会影响尼古丁强化或导致药物的认知和情感副作用。在这项研究中，我们确定伐尼克兰是否像尼古丁一样可以刺激突触前GABA的释放。使用全细胞膜片钳技术，我们测量了GABAAR介导的异步，自发的微型抑制性突触后电流（mIPSC）在急性脑切片从两个重要的学习和记忆，海马和基底前脑的大脑区域。单独应用伐尼克兰（10 μM）和尼古丁（10 μM）均导致海马CA 1锥体神经元和内侧隔/斜角带（MS/DB）神经元中mIPSC的振幅小幅但显著增加，以及频率显著增强。MS/DB神经元的一个独特的亚群显示频率下降。在尼古丁的存在下，伐尼克兰有效地衰减海马mIPSC频率的预期增强像一个竞争性拮抗剂。然而，在MS/DB中，伐尼克兰仅部分减弱尼古丁的作用。通过在暴露于伐尼克兰的切片中加入尼古丁来颠倒药物应用的顺序几乎没有效果。伐尼克兰与尼古丁一样，刺激突触前GABA释放，并通过减弱海马和基底前脑中尼古丁刺激的释放发挥部分激动剂作用。这些影响可能会影响认知功能
The FDA approved smoking cessation aid varenicline can effectively attenuate nicotine-stimulated dopamine release. Varenicline may also exert important actions on other transmitter systems that also influence nicotine reinforcement or contribute to the drug’s cognitive and affective side effects. In this study, we determined if varenicline, like nicotine, can stimulate presynaptic GABA release. Using whole-cell patch-clamp techniques, we measured GABAAR-mediated asynchronous, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in acute brain slices from two brain regions important for learning and memory, the hippocampus and basal forebrain. Both varenicline (10 μM) and nicotine (10 μM) applications alone resulted in small but significant increases in amplitude, as well as robustly enhanced frequency of mIPSCs in hippocampal CA1 pyramidal neurons and medial septum /diagonal band (MS/DB) neurons. A unique subpopulation of MS/DB neurons showed decreases in frequency. In the presence of nicotine, varenicline effectively attenuated the expected enhancement of hippocampal mIPSC frequency like a competitive antagonist. However, in the MS/DB, varenicline only partially attenuated nicotine’s effects. Reversing the order of drug application by adding nicotine to varenicline-exposed slices had little effect. Varenicline, like nicotine, stimulates presynaptic GABA release, and also exerts a partial agonist action by attenuating nicotine-stimulated release in both the hippocampus and basal forebrain. These effects could potentially affect cognitive functions
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影响因子：
5.8
作者：
Quik M;Perez XA;Grady SR
通讯作者：
Grady SR
DOI：
10.1124/jpet.105.100552
发表时间：
2006-08-01
影响因子：
3.5
作者：
DuBois, Dustin W.;Perlegas, Andreas;McCool, Brian A.
通讯作者：
McCool, Brian A.
影响因子：
5.5
作者：
Henderson, Z;Boros, A;Halasy, K
通讯作者：
Halasy, K
影响因子：
2.5
作者：
LESTER, RAJ;DANI, JA
通讯作者：
DANI, JA
DOI：
10.1016/j.devbrainres.2004.06.017
发表时间：
2004-09-17
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
DuBois, DW;Parrish, AR;Frye, GD
通讯作者：
Frye, GD