Inhibition of PKC disrupts addiction-related memory.
Inhibition of PKC disrupts addiction-related memory.
复制标题
DOI：
10.3389/fnbeh.2014.00070
复制
发表时间：
2014
影响因子：
3
通讯作者：
Anagnostaras SG
中科院分区：
文献类型：
--
作者：
Howell KK;Monk BR;Carmack SA;Mrowczynski OD;Clark RE;Anagnostaras SG
非典型PKC亚型PKM β和PKCλ被认为是长时记忆（LTM）的重要底物。最近已证明抑制这些亚型足以损害长时程增强的表达和维持。此外，假底物抑制剂zeta抑制肽（ZIP）可以有效地阻断PKM β和PKCλ，先前已被证明会破坏联想记忆;关于它对成瘾相关的病理性非联想记忆形式的影响，人们知之甚少。记忆和成瘾的神经和分子基质最近被认为是重叠的。在这里，我们使用ZIP来破坏PKM β和PKCλ的活性，以检查它们在可卡因致敏中的作用，可卡因致敏是一种非联想的成瘾相关记忆，被认为是从偶然到病理性药物使用的转变的基础。我们研究了连续和急性管理ZIP的影响。即使是一个单一的应用程序的ZIP阻止致敏的发展，持续抑制使用渗透泵产生了几乎完全封锁的致敏。此外，ZIP的单次应用显示减少膜结合AMPAR表达。这些结果表明，非典型PKC亚型在非联想记忆和可卡因成瘾中的一个新的，关键的作用。
The atypical PKC isoforms, PKMζ and PKCλ have been proposed as integral substrates of long-term memory (LTM). Inhibition of these isoforms has recently been demonstrated to be sufficient for impairing the expression and maintenance of long-term potentiation. Additionally, the pseudosubstrate inhibitor, zeta inhibitory peptide (ZIP), which effectively blocks PKMζ and PKCλ, has previously been shown to disrupt associative memory; very little is known about its effects on pathological nonassociative forms of memory related to addiction. The neural and molecular substrates of memory and addiction have recently been argued to overlap. Here, we used ZIP to disrupt PKMζ and PKCλ activity to examine their role in cocaine sensitization, a nonassociative, addiction-related memory argued to underlie the transition from casual to pathological drug use. We examined the effects of both continuous and acute administration of ZIP. Even a single application of ZIP blocked the development of sensitization; sustained inhibition using osmotic pumps produced an almost complete blockade of sensitization. Further, a single application of ZIP was shown to reduce membrane-bound AMPAR expression. These results demonstrate a novel, critical role for the atypical PKC isoforms in nonassociative memory and cocaine addiction.
登录
查看更多内容
影响因子：
34.7
作者：
Lisman, John;Yasuda, Ryohei;Raghavachari, Sridhar
通讯作者：
Raghavachari, Sridhar
影响因子：
16.2
作者：
Lüscher C;Malenka RC
通讯作者：
Malenka RC
影响因子：
5.2
作者：
Lee AM;Messing RO
通讯作者：
Messing RO
DOI：
10.1523/jneurosci.5884-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li YQ;Xue YX;He YY;Li FQ;Xue LF;Xu CM;Sacktor TC;Shaham Y;Lu L
通讯作者：
Lu L
影响因子：
3.8
作者：
Jang, CG;Rockhold, RW;Ho, IK
通讯作者：
Ho, IK