Serotonin 1A Receptor (5-HT1AR) Knockout Mouse: Anxiety Model
- *Abstract
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Since their introduction in the early 1960s, benzodiazepines such as Valium and Librium have dominated treatment of anxiety states. However, benzodiazepines have several side effects. It has been established that medium- and long-term use of benzodiazepines is associated with physical dependence and withdrawal syndrome in a significant portion of patients. Another shortcoming of benzodiazepines is that they are not very effective against certain forms of anxiety disorders. Physical dependence and other side effects of benzodiazepines as well as their restricted efficacy clearly indicated the necessity to develop novel anxiolytics.
However, screening and identifying novel drugs suffer from problems associated with current animal models. Because all animal models developed for screening anxiolytics have been validated by benzodiazepines, these tests are optimized for finding benzodiazepine-like drugs. Also, these tests are based on abolishing natural aversion and fear in normal animals which may not be related to relieving unrealistic or excessive anxiety in pathological anxiety.
Genetic inactivation of the serotonin 1A receptor (5-HT1AR) in mice resulted in heightened anxiety. This mouse strain is insensitive to the anxiolytic effect of benzodiazepines. Similar to human anxiety disorders, receptor inactivation in these mice results in a condition that is limited to the above mentioned anxiety-like behavioral abnormalities and does not effect development, reproduction, and lifespan. The two main advantages of this animal model are: -- 5-HT1AR deficient mice represent an etiological animal model of anxiety -- Because they are insensitive to benzodiazepines, 5-HT1AR deficient mice will be useful to selectively identify non-benzodiazepine anxiolytics.
- *Licensing
- Dan-Oscar Antsonda429@cornell.edu212-746-1297
- 其他
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- Increased anxiety of mice lacking the serotonin 1A receptor. Proc Natl Acad Sci USA 1998 Sep 1;95(18): p10734-9
- Genetic inactivation of the Serotonin(1A) receptor in mice results in downregulation of major GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety. J Neurosci 2000 Apr 15;20(8): p2758-65
- 國家/地區
- 美國
