Gene tinkering hikes fear and anxiety in mice 

 Since only a portion of the people exposed to traumatic events develop anxiety disorders, researchers suspect that some type of genetic vulnerability contributes to these distressing conditions.

 Rodents may yield valuable clues to the presumably inherited roots of severe anxiety reactions, a new study suggests. Mice deprived of a gene that facilitates transmission of specific chemical messages in the brain represent a potential animal model of anxiety-prone people, reports a team of neuroscientists led by Florence Crestani and Hanns Mohler of the University of Zurich.

 Experimental deletion of the mouse gene leads to a marked drop in the number of molecular receptors for a neurotransmitter known as GABA, the researchers contend. GABA dampens the activity of brain areas-such as the amygdala and hippocampus-implicated in fear and anxiety. Antianxiety drugs, such as Valium, work by activating the GABA receptors that Crestani and Mohler's group focused on.

 An inherited shortage of these signal entry points into brain cells may predispose people to develop anxiety disorders in response to stressful or traumatic experiences, the scientists propose in the September Nature Neuroscience.

 They first examined brain slices taken from mice either retaining or missing a copy of the GABA-receptor gene. Those missing the gene had many fewer GABA receptors, mainly in the hippocampus, amygdala, and frontal brain.

 Gene-deprived mice showed greater anxiety on several laboratory tests, the scientists say. For instance, in an elevated maze, they usually avoided walking along passages with no walls, unlike their DNA-intact comrades.

 Receptor-poor mice also learned more quickly to react fearfully to a tone that regularly preceded a foot shock by 1 second, as well as to a light that occasionally appeared just before the tone and foot shock. This shows that, like anxiety-ridden humans, the genetically altered mice feel distressed even by events with a tenuous link to an actual threat, the scientists say.

 Mutant mice performed as well on spatial learning tasks as receptor-rich mice did, indicating that the genetic loss influenced only anxiety. Moreover, the mutant mice became far less fearful after receiving injections of a Valium-like drug.

 These mice "offer the promise of a genetic model of the anxiety-predisposed human," remark neurobiologist Stephan G. Anagnostaras of the University of California, Los Angeles and his colleagues in the same journal. Such mice may prove useful in testing new antianxiety drugs, they say.

 Brain mechanisms by which the gene deletion pumps up anxiety remain uncertain, Anagnostaras' group notes.

 Psychiatrist Kenneth S. Kendler of Virginia Commonwealth University in Richmond commends the new study as "beautiful work," although he says it's difficult to compare the mutant mice to people suffering from most anxiety disorders. The rodents, however, may help scientists understand the constant sense of anxiety and fright experienced by individuals diagnosed with generalized anxiety disorder, says Kendler.