Narp regulates long-term aversive effects of morphine withdrawal

作者：Reti Irving M^*; Crombag Hans S; Takamiya Kogo; Sutton Jeffrey M; Guo Ning; Dinenna Megan L; Huganir Richard L; Holland Peter C; Baraban Jay M

来源：Behavioral Neuroscience, 2008, 122(4): 760-768.

DOI：10.1037/a0012514

• immediate early gene
• naltrexone
• place aversion
• AMPA
• amygdala

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp, knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction.

• 出版日期2008-8