Even though benzodiazepines are prescribed to women almost twice as often as to men, there is relatively little information regarding the effects of these medications in women, particularly with respect to their potential for misuse and/or abuse. Although the incidence of abuse of these drugs is relatively low in the general population, they can be a significant problem for vulnerable individuals. A number of factors can contribute to this vulnerability, including pharmacological history, as well as environmental, genetic and organismic variables.
The aim of this five year proposal is to extend our current knowledge about the abuse liability of anxiolytics to women, focusing on specific subpopulations of non-drug abusing women who may be more vulnerable to the reinforcing effects of these drugs: l) women who have family histories of alcoholism (genetic): 2) women who are moderate social drinkers (pharmacological history): 3) women with generalized anxiety disorder (organismic): and 4) women with significant premenstrual symptoms (organismic). Well-established laboratory methods will be used to assess the abuse liability of anxiolytics in each of these subpopulations. Females meeting criteria for one of the vulnerable subpopulations under study and respective matched control subjects will participate. Two experiments will be carried out for each subpopulation. The first experiment, a double-blind, placebo-controlled Dose-Effect Experiment, will repeatedly assess multiple concurrent measures including subjective, performance, and physiological effects of two anxiolytics. The second experiment, a Choice Experiment, will evaluate the reinforcing effects of these anxiolytics to determine if any of these subpopulations of females are more susceptible to the reinforcing effects of these drugs. The benzodiazepine alprazolam, shown to have abuse potential in male sedative abusers, will be the positive control and the non-benzodiazepine buspirone, shown to have relatively low abuse potential, will be the negative control. The possible role of environmental stress in modulating the behavioral effects of these anxiolytics will be investigated in both experiments by having subjects perform behaviorally-demanding tasks. The paucity of research focused on women's health issues includes the area of substance abuse. The proposed studies will empirically identify vulnerable subpopulations of females who are at risk to abuse anxiolytics. The results should increase our understanding of the relevant variables contributing to this increased vulnerability. In addition to differentiating among various factors which may contribute to the likelihood that a woman will abuse anxiolytics, these studies will provide important information for the development of appropriate interventions and/or treatments for these vulnerable individuals.
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