Changes in PKA activity and GSα and Golfα levels after amphetamine- and cocaine-induced behavioral sensitization
Changes in PKA activity and GSα and Golfα levels after amphetamine- and cocaine-induced behavioral sensitization
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DOI：
10.1002/syn.10301
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发表时间：
2004-03-15
期刊：
影响因子：
2.3
通讯作者：
McDougall, SA
中科院分区：
文献类型：
--
作者：
Crawford, CA;Choi, FY;McDougall, SA
cAMP信号转导系统中的神经适应在精神兴奋剂诱导的行为敏化中起关键作用。然而，与这一假设相关的研究提供了相互矛盾的证据，因为重复的可卡因和安非他明治疗交替报告增加或减少背侧纹状体和背侧纹状体中的蛋白激酶A（PKA）活性。为了调和这些不同的发现，PKA活性和刺激性G-蛋白亚基，G（Salpha）和G（olfalpha），大鼠接受致敏诱导方案的安非他明或可卡因后进行测量。结果表明，连续7天注射安非他明或可卡因产生运动致敏，并导致减少在β-PKA活性。在测试当天注射安非他明也降低了背侧纹状体PKA活性。G（Salpha）水平不受精神兴奋剂暴露的影响，而G（olfalpha）水平在安非他明或可卡因预处理后显着下降。因为重复的安非他明和可卡因治疗都诱导行为敏化和降低的PKA活性，看来，精神兴奋剂诱导的PKA活性的增加是不必要的行为敏化的最终表达。(C)2003 Wiley-Liss，Inc.
Neuroadaptations in the cAMP signal transduction system have been proposed to play a critical role in psychostimulant-induced behavioral sensitization. Studies relevant to this hypothesis have provided conflicting evidence, however, because repeated cocaine and amphetamine treatment has been alternately reported to either increase or decrease protein kinase A (PKA) activity in the nucleus accumbens and dorsal striatum. In an attempt to reconcile these disparate findings, PKA activity and the stimulatory G-protein subunits, G(Salpha) and G(olfalpha), were measured after rats had received a sensitization-inducing regimen of amphetamine or cocaine. Results showed that seven consecutive daily injections of amphetamine or cocaine produced locomotor sensitization and caused a reduction in accumbal PKA activity. A challenge injection of amphetamine on the test day also reduced dorsal striatal PKA activity. G(Salpha) levels were unaffected by psychostimulant exposure, while G(olfalpha) levels in the nucleus accumbens declined significantly after amphetamine or cocaine pretreatment. Because repeated amphetamine and cocaine treatment both induced behavioral sensitization and decreased accumbal PKA activity, it appears that psychostimulant-induced increases in PKA activity are not necessary for the ultimate expression of behavioral sensitization. (C) 2003 Wiley-Liss, Inc.