Your heart is racing, you're sweating, trembling, feel exhausted and cannot breathe for over 20 million Americans who face chronic and excessive anxiety each day, these physical reactions to real or imagined danger are well known. Prescription anxiolytics (anxiety-reducing medications), such as clonazepam (Klonopin), alprazolan (Xanax) and lorazepam (Ativan) have been widely employed in the treatment of anxiety disorders to relieve these physical symptoms while other forms of behavioral therapy proceed, however their long-term use is discouraged due to their somewhat addictive potential and sedating side effects. A study reported in the October 1 issue of the Journal of Clinical Investigation (JCI) by Dr. Robert Messing and colleagues from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco, reveals that mice lacking a form of the enzyme protein kinase C (PKCe) are supersensitive to their brain's own calming neurosteroids and exhibit reduced anxiety. The authors suggest that inhibitors of PKCe may be useful in treating anxiety.

Severe and excessive anxiety is associated with irregular levels of neurotransmitters in the brain. These chemicals ferry signals between nerve endings and regulate the activity of nerve cells. An inhibitory agent within the central nervous system, gamma aminobutyric acid (or GABA), is the most important blocker of this communication between neurons and helps control nerve cells from firing too fast. The GABAA receptor forms a closed channel that is triggered to open upon the binding of GABA. A rush of chloride ions through the open channel into the cell inhibits the release of neurotransmitters. In this way, drugs such as barbiturates and the benzodiazepines mentioned above decrease anxiety, induce sleep and even anesthesia.

Earlier studies by this group reveal that mice lacking the gene for PKCe have an increased sensitivity to alcohol, benzodiazepines and barbiturates. These observ
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Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
2-Oct-2002

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