DOPAMINERGIC ANTAGONISTS PREVENT LONG-TERM MAINTENANCE OF POSTTETANIC LTP IN THE CA1 REGION OF RAT HIPPOCAMPAL SLICES

DOPAMINERGIC ANTAGONISTS PREVENT LONG-TERM MAINTENANCE OF POSTTETANIC LTP IN THE CA1 REGION OF RAT HIPPOCAMPAL SLICES
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DOI:
10.1016/0006-8993(90)91578-5
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发表时间:
1990-07-02
期刊:
影响因子:
2.9
通讯作者:
MATTHIES, H
MATTHIES, H
中科院分区:
医学3区
文献类型:
--
作者:
FREY, U;SCHROEDER, H;MATTHIES, H

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在大鼠海马脑片的CA1细胞上研究了多巴胺能机制在强直后长时程增强(LTP)的诱导和维持中的作用。在以3串100个脉冲(100Hz)且串间隔为10分钟进行强直刺激期间,存在浓度为1μM的多巴胺受体阻断剂多潘立酮,既不影响突触传递,也不影响LTP的诱导。然而,群体峰电位和群体兴奋性突触后电位(EPSP)的增强逐渐减弱,因此在起始约4小时后与对照LTP有显著差异,并在强直刺激后约7 - 8小时达到未强直刺激对照的水平。在强直刺激期间同时存在1μM的阿扑吗啡可消除多潘立酮的这种作用,表明其作用具有特异性的多巴胺拮抗性质。同样,在强直刺激期间分别存在浓度为1μM的多巴胺拮抗剂舒必利和氟哌噻吨,也可阻止晚期LTP维持的发生。在预孵育期间预加载后,对灌流脑片中2分钟组分的[14C]多巴胺进行测定,结果显示,以0.33Hz对谢弗侧支进行低频刺激不影响多巴胺的自发外流,而100Hz的脉冲串进行强直刺激则产生显著增强的释放。这些观察结果表明,强直刺激期间和之后立即的多巴胺能影响至少对诱导突触后机制有额外作用,这些机制有助于晚期、持久的增强维持。这些结果也支持LTP存在不同后续阶段的假设。
The involvement of dopaminergic mechanisms in the induction and maintenance of posttetanic long-term potentiation (LTP) was investigated on CA1 cells of rat hippocampal slices. The presence of the dopamine receptor blocker domperidone in a concentration of 1 .mu.M during tetanization with 3 trains of 100 impulses (100 Hz) and a train interval of 10 min influences neither the synaptic transmission nor the induction of LTP. However, the potentiation of both the population spike and the population EPSP gradually decreases, thus significantly differing from control LTP about 4 h after initiation and reaching the level of non-tetanized controls about 7-8 h after tetanization. The simultaneous presence of 1 .mu.M ampomorphine during tetanization abolishes this effect of domperidone indicating the specific dopaminolytic nature of its action. Also the presence of the dopamine antagonists sulpiride and fluphenthixol, respectively, in a concentration of 1 .mu.M during tetanization likewise prevents the occurrence of the late LTP maintenance. The determination of [14C)dopamine in 2 min fractions from the superfused slices after preloading during a preincubation period revealed that a low frequency stimulation of the Schaffer collaterals with 0.33 Hz does not influence the spontaneous efflux of dopamine, whereas the tetanization with an impulse train of 100 Hz produces a singificantly enhanced release. The observations suggest that dopaminergic influences during and immediately after tetanization at least additionally contribute to the induction of postsynaptic mechanisms subserving a late, long-lasting maintenance of potentiation. The results also support the assumed existence of different subsequent stages of LTP.