GABAA Receptor α1 Subunit Knockout Mice: A Novel Model of Essential Tremor

Deletion of GABA A receptor α1 subunits in mice results in a phenotype of kinetic tremor that mimics certain features of essential tremor disease. The GABA A benzodiazepine receptor agonist diazepam and the GABAergic neuroactive steroid allopregnanolone exacerbate the tremor, whereas ethanol completely inhibits the tremor. Since the etiology of essential tremor is unknown, this animal model of genetic essential tremor may lead to an understanding of the pathophysiology of the disease and provide a valuable model system to develop therapeutic interventions. Although tremor is often associated with neurological conditions, such as Parkinson's disease, it is capable of manifesting itself in many other ways. Essential tremor, the most common of the tremor disorders, is a primary condition independent of any overlying disorder. Tremor is also commonly associated with substance withdrawal, and it is often a side effect of various drug treatments. The current studies investigating the ability of GABAergic drugs to modulate pathological tremor have provided direction for future experimental procedures investigating the pathology of the knockout tremor. Future studies may include drugs that mediate their actions through other sites of ethanol action. With continuing research on the mechanisms for genetic essential tremor and possible experimental treatments, a cure for essential tremor and other tremor behaviors may be realized in the near future.