Inhibition of phosphodiesterase-4 decreases ethanol intake in mice.
Inhibition of phosphodiesterase-4 decreases ethanol intake in mice.
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DOI：
10.1007/s00213-011-2290-8
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发表时间：
2011-11
影响因子：
3.4
通讯作者：
Zhang, Han-Ting
中科院分区：
文献类型：
--
作者：
Hu, Wei;Lu, Tina;Chen, Alan;Huang, Ying;Hansen, Rolf;Chandler, L. Judson;Zhang, Han-Ting
关键词：
环磷酸腺苷（cAMP）-蛋白激酶A（PKA）信号转导与乙醇消耗的调节有关。磷酸二酯酶-4（PDE 4）特异性水解cAMP，并在控制脑细胞内cAMP水平方面发挥关键作用。然而，PDE 4在乙醇消耗中的作用仍然未知。研究PDE 4是否参与调节乙醇摄入。使用两瓶选择范例来评估用选择性PDE 4抑制剂咯利普兰或Ro 20-1724处理的C57 BL/6 J小鼠中乙醇、蔗糖和奎宁的摄入;还使用咯利普兰处理的小鼠中的旷场试验来监测运动活性。给药（i. p.）咯利普兰（0.25和0.5 mg/kg）或Ro 20-1724（10 mg/kg）的剂量降低了60- 80%的乙醇摄入量和偏好，但没有改变总的液体摄入量。相比之下，咯利普兰即使在0.5 mg/kg的较高剂量下也不能影响蔗糖或奎宁的摄入、酒精诱导的镇静或血液乙醇消除。在0.5 mg/kg时，咯利普兰确实降低了自发活动，但效果仅持续约40 min，这不太可能影响饮酒行为。这些结果表明，PDE 4是减少乙醇摄入的药物的新靶点; PDE 4抑制剂可用于治疗酒精依赖。
Cyclic AMP (cAMP)-protein kinase A (PKA) signaling has been implicated in the regulation of ethanol consumption. Phosphodiesterase-4 (PDE4) specifically hydrolyzes cAMP and plays a critical role in controlling intracellular cAMP levels in the brain. However, the role of PDE4 in ethanol consumption remains unknown. To examine whether PDE4 was involved in regulating ethanol intake. The two-bottle choice paradigm was used to assess intake of ethanol, sucrose, and quinine in C57BL/6J mice treated with the selective PDE4 inhibitor rolipram or Ro 20-1724; locomotor activity was also monitored using the open-field test in mice treated with rolipram. Administration (i.p.) of either rolipram (0.25 and 0.5 mg/kg) or Ro 20-1724 (10 mg/kg) reduced ethanol intake and preference by 60-80%, but did not alter total fluid intake. In contrast, rolipram even at the higher dose of 0.5 mg/kg was not able to affect intake of sucrose or quinine, alcohol-induced sedation, or blood ethanol elimination. At 0.5 mg/kg, rolipram did decrease locomotor activity, but the effect only lasted for approximately 40 min, which did not likely affect behavior of ethanol drinking. These results suggest that PDE4 is a novel target for drugs that reduce ethanol intake; PDE4 inhibitors may be used for treatment of alcohol dependence.
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DOI：
10.1097/01.alc.0000141809.53115.71
发表时间：
2004-10-01
影响因子：
3.2
作者：
Fee, JR;Sparta, DR;Thiele, TE
通讯作者：
Thiele, TE
DOI：
10.1523/jneurosci.5236-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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通讯作者：
Zhang HT
环-AMP 依赖性蛋白激酶 a 在大鼠脑核中的功能下降： 在大鼠饮酒而非焦虑样行为中发挥作用
影响因子：
7.6
作者：
Misra, Kaushik;Pandey, Subhash C.
通讯作者：
Pandey, Subhash C.
DOI：
10.1152/ajpgi.90232.2008
发表时间：
2008-10-01
影响因子：
4.5
作者：
Gobejishvili, Leila;Barve, Shirish;McClain, Craig
通讯作者：
McClain, Craig
影响因子：
3.6
作者：
Knapp, CM;Foye, MM;Kornetsky, C
通讯作者：
Kornetsky, C