Increased sensitivity to alprazolam in females with a paternal history of alcoholism

Rationale: Few studies have directly examined the effects of benzodiazepine s in individuals with a family history of alcoholism, particularly women, t o determine whether they are differentially sensitive to their effects. Obj ectives: To deter-mine whether females with a confirmed paternal history of alcoholism (FHP; n=14) were differentially sensitive to the mood and perfo rmance effects of alprazolam and buspirone compared with females without a first-degree family history of alcoholism (FHN; n=14). Methods. The acute e ffects of placebo, alprazolam (0.25, 0.50, 0.75 mg), and buspirone (5. 10, 15 mg) were evaluated using a double-blind, placebo-controlled outpatient d esign. Drug effects were assessed using performance tasks, observer ratings of drug effect, and subjective ratings of mood, drug strength, and drug li king. Results: Alprazolam impaired performance in a dose-related manner on all performance tasks for both groups of females, whereas buspirone had min imal effects on performance. The highest dose of alprazolam impaired the re sponse to the digit symbol substitution test (DSST), digit recall, and word memory more in FHP females than in RIN females. Further, performance on th e DSST and immediate word recall was able to accurately predict family hist ory status. Correspondingly, FHP women reported greater increases in "diffi culty concentrating" and "unmotivated" and greater decreases in items such as positive mood following alprazolam than FHN women. In cont! ast, alprazo lam produced similar dose-related increases in subject-rated and observerra ted drug strength ratings in both groups of females. Lastly, th;re was no e vidence of an increase in ratings of drug liking in either group following alprazolam. Conclusions: In contrast to many previous findings with RIP mal es, these results suggest that FHP females may be more sensitive to the per formance-impairing effects and negative subjective effects of alprazolam.