? ? Drugs of abuse, such as morphine, cause long-lasting changes that underlie behaviors associated with drug addiction. It has been proposed that these changes are similar to those underlying memory formation. In agreement, many compounds that impair memory formation and inhibit memory-associated molecular pathway also attenuate drug tolerance and dependence. Newly formed memories are initially labile and require protein synthesis in order to be consolidated into a long-term memory. Furthermore, when a consolidated memory is recalled, it again becomes labile and requires protein synthesis in order to be maintained. The requirement for protein synthesis of addictive memories is virtually unknown. Here we propose to address several fundamental questions that will target the protein synthesis-dependent processes of addictive memory and other addictive behaviors. The results of these experiments will lay a foundation for further studies, which will examine molecules, pathways and pharmacological intervention in addiction. These investigations may produce significant breakthroughs that could help in the development of new therapies for drug addiction.
The Aims of this project are: 1) To determine the temporal and anatomical specificity of protein synthesis requirement in addictive contextual associations. 2) To determine the behavioral specificity of the requirement for protein synthesis in addiction. 3) To determine whether the requirement for protein synthesis is a general mechanism underlying addictive memories. ? ?
| Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana et al. (2010) Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner. Proc Natl Acad Sci U S A 107:12345-50 |
| Alberini, Cristina M (2008) The role of protein synthesis during the labile phases of memory: revisiting the skepticism. Neurobiol Learn Mem 89:234-46 |
| Milekic, Maria H; Brown, Sheena D; Castellini, Claudia et al. (2006) Persistent disruption of an established morphine conditioned place preference. J Neurosci 26:3010-20 |
