Abstract: The present invention is directed to a screening mechanism for identifying members of the general population at increased risk for alcoholism and premenstrual syndrome. The screening mechanisms may be used to measure the expression of the ?4?2? GABAA receptors, in order to identify members of the general population as having an increased sensitivity to lower concentrations alcohol coupled with a decrease sensitivity to higher concentrations of alcohol, a scenario frequently found in patients suffering from alcoholism and premenstrual anxiety. Methods of screening for drugs which decrease expression of the ?4?2? subunit of GABAA are also provided.

Abstract: The present invention provides methods for treating anxiety or irritability in a subject. The methods comprise administering to the subject an effective amount of an antagonist of allopregnanolone (THP), or a regulator which decreases expression of the alpha 4 subunit of GABA such as gabadoxbol (THIP), or a vector comprising an isolated nucleic acid molecule encoding a mutant alpha 4 subunit GABAA receptor protein having a neutral or non-basic amino acid residue substituted for the arginine residue at position 353 of the wild type mature protein, wherein this nucleic acid molecule is operably linked to a promoter which functions in the human brain. Such methods are useful in treating a subject undergoing a stage such as entering or having reached puberty, suffering from pre-menstrual syndrome (PMS), entering or having reached post-partem stage, entering or having reached menopause, and/or suffering from chronic stress.

Abstract: The present invention is directed to a screening mechanism for identifying members of the general population at increased risk for alcoholism and premenstrual syndrome. The screening mechanisms may be used to measure the expression of the ?4?2? GABAA receptors, in order to identify members of the general population as having an increased sensitivity to lower concentrations alcohol coupled with a decrease sensitivity to higher concentrations of alcohol, a scenario frequently found in patients suffering from alcoholism and premenstrual anxiety. Methods of screening for drugs which decrease expression of the ?4?2? subunit of GABAA are also provided.