| First Author | Maul B | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 11 | Pages | e50187 |
| PubMed ID | 23185571 | Mgi Jnum | J:195579 |
| Mgi Id | MGI:5484826 | Doi | 10.1371/journal.pone.0050187 |
| Citation | Maul B, et al. (2012) Genetic deficiency in neprilysin or its pharmacological inhibition initiate excessive stress-induced alcohol consumption in mice. PLoS One 7(11):e50187 |
| abstractText | Both acquired and inherited genetic factors contribute to excessive alcohol consumption and the corresponding development of addiction. Here we show that the genetic deficiency in neprilysin [NEP] did not change the kinetics of alcohol degradation but led to an increase in alcohol intake in mice in a 2-bottle-free-choice paradigm after one single stress stimulus (intruder). A repetition of such stress led to an irreversible elevated alcohol consumption. This phenomenon could be also observed in wild-type mice receiving an orally active NEP inhibitor. We therefore elucidated the stress behavior in NEP-deficient mice. In an Elevated Plus Maze, NEP knockouts crossed more often the area between the arms, implicating a significant stronger stress response. Furthermore, such animals showed a decreased locomotor activity under intense light in a locomotor activity test, identifying such mice to be more responsive in aversive situations than their wild-type controls. Since the reduction in NEP activity itself does not lead to significant signs of an altered alcohol preference in mice but requires an environmental stimulus, our findings build a bridge between stress components and genetic factors in the development of alcoholism. Therefore, targeting NEP activity might be a very attractive approach for the treatment of alcohol abuse in a society with increasing social and financial stress. |
