Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats.
Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats.
复制标题
多巴胺敏感信号传导介质调节精神兴奋剂诱导的大鼠超声发声行为。
DOI：
10.1016/j.bbr.2015.08.008
复制
发表时间：
2016
影响因子：
2.7
通讯作者：
Undieh,AshiwelS
中科院分区：
文献类型：
--
作者：
Williams,StaceyN;Undieh,AshiwelS
中脑边缘多巴胺系统在精神兴奋剂诱导的啮齿类动物超声波发声（USV）行为中起着重要作用。在该系统中，精神兴奋剂提高多巴胺的突触浓度，从而导致D1样和D2样亚家族内突触后多巴胺受体的过度激活。多巴胺受体刺激激活几个跨膜信号传导系统和同源细胞内介质;转录因子的下游激活然后将信息从受体激活传递到细胞和生理功能的适当调节。我们先前发现可卡因诱导的USV行为与神经营养因子BDNF的表达增强有关。像可卡因一样，安非他明也会增加突触多巴胺水平，尽管主要是通过促进多巴胺释放。因此，在本研究中，我们研究了安非他明和可卡因是否同样激活多巴胺相关的信号级联，以调节细胞内介质，导致USV行为的诱导。结果表明，安非他明可使50 kHz超声波的发射增加，这种作用可被D1受体拮抗剂SCH 23390阻断。与可卡因类似，安非他明增加了离散脑区BDNF蛋白的表达，而用trkB神经营养因子受体抑制剂K252 a预处理，显着减少安非他明诱导的USV行为。用H89抑制cyclic-AMP/PKA信号传导或用U 73122抑制PLC信号传导显著阻断了急性和亚慢性安非他明诱导的USV行为。相反，药理学抑制任一途径增强可卡因诱导的USV行为。虽然可卡因和安非他明类似地调节神经营养因子的表达和USV，这些精神兴奋剂差异激活多巴胺受体亚型或其他单胺能系统的分子机制可能是负责行为反应的不同方面。
The mesolimbic dopamine system plays a major role in psychostimulant-induced ultrasonic vocalization (USV) behavior in rodents. Within this system, psychostimulants elevate synaptic concentrations of dopamine thereby leading to exaggerated activation of postsynaptic dopamine receptors within the D1-like and D2-like subfamilies. Dopamine receptor stimulation activate several transmembrane signaling systems and cognate intracellular mediators; downstream activation of transcription factors then conveys the information from receptor activation to appropriate modulation of cellular and physiologic functions. We previously showed that cocaine-induced USV behavior was associated with enhanced expression of the neurotrophin BDNF. Like cocaine, amphetamine also increases synaptic dopamine levels, albeit primarily through facilitating dopamine release. Therefore, in the present study we investigated whether amphetamine and cocaine similarly activate dopamine-linked signaling cascades to regulate intracellular mediators leading to induction of USV behavior. The results show that amphetamine increased the emission of 50 kHz USVs and this effect was blocked by SCH23390, a D1 receptor antagonist. Similar to cocaine, amphetamine increased BDNF protein expression in discrete brain regions, while pretreatment with K252a, a trkB neurotrophin receptor inhibitor, significantly reduced amphetamine-induced USV behavior. Inhibition of cyclic-AMP/PKA signaling with H89 or inhibition of PLC signaling with U73122 significantly blocked both the acute and subchronic amphetamine-induced USV behavior. In contrast, pharmacologic inhibition of either pathway enhanced cocaine-induced USV behavior. Although cocaine and amphetamine similarly modulate neurotrophin expression and USV, the molecular mechanisms by which these psychostimulants differentially activate dopamine receptor subtypes or other monoaminergic systems may be responsible for the distinct aspects of behavioral responses.