This grant proposes five years of research to investigate the behavioral effects of drugs with abuse liability in women. Experimental procedures to be used have been established with male subjects in residential settings to measure simultaneously the effects of drugs of abuse on multiple dimensions of human behavior, including learning ability, reaction time, temporal discrimination, psychomotor performance, food consumption, social behavior, physiological reactivity, tobacco cigarette smoking behavior, mood, impulsivity, and subjective report of drug effects. Separate groups of studies will be completed with women of different ages. The first group of studies will be completed with healthy normal women of child-bearing age (i.e., 21-40). Dose-response determinations will be completed at fixed times during the menstrual cycle in order to determine the influence os regularly-occurring fluctuations in hormone levels on the behavioral effects of drugs. Results will be compared with those obtained from a matched group of male subjects in order to assess sex differences in drug effects. The second group of studies will be completed with health post-menopausal women (i.e., 55-65). Dose-response determinations will again be completed before and at fixed times during menstrual cycles occurring after initiation of estrogen/progesterone replacement therapy in order to assess the influence of experimenter-administered hormones on the behavioral effects of drugs with abuse liability. Again, results will be compared with those obtained with a matched group of male subjects in order to asses gender differences in drug effects. Finally, dose- response determinations completed with the control groups of male subjects (age ranges of 21-40 vs. 55-65) will be compared in order to assess the influence of age on the behavioral effects of drugs. The results of these studies will provide information on a number of important and understudied issues. First, these studies will determine the behavioral effects of drugs of abuse in women. Second, these studies will examine critical yet largely ignored issues regarding the potential modulation of the behavioral effects of drugs with abuse liability by hormones. Third, these studies will generate important information regarding the behavioral effects of hormone-replacement therapy in post- menopausal women, and the potential effects of such therapy on behavioral response to drugs. Fourth, the studies will investigate changes in the behavioral effects of drugs with abuse liability as a function of age. Few of these issues have been studied in humans. In addition, these data will be useful for determining the generalizability of studies completed previously with male subjects and for establishing conditions and controls to enhance the generality and utility of future studies of the behavioral effects of drugs on humans.
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NIH ExPorter