Gender differences in response to lorazepam in a human drug discrimination study

Gender differences in the discriminative stimulus properties of drugs of abuse have sometimes been reported, although we have previously found no differences in subjective or discriminative responses in human subjects acquiring an alcohol discrimination. The aim of the present work was to determine if there were gender differences in the effects of lorazepam, a benzodiazepine-receptor agonist which substituted for the alcohol stimulus in trained social drinkers. Volunteers who had already acquired an alcohol (0.2g/kg) placebo discrimination were administered (double-blind) either placebo (nine females, nine males) or lorazepam 2mg (six females, six males). They then sampled a series of five drinks and rated each one for likeness to the training stimulus (the generalization response). In addition they completed rating scales for subjective effects and the Digit Symbol Substitution Test (DSST). Lorazepam substituted for the alcohol stimulus equally in both sexes and increased associated scores for lightheadedness. Females however, showed a much greater DSST performance impairment following lorazepam, compared with males. This effect was independent of body weight differences and sedation. These results are discussed in the light of current knowledge of gender differences in response to drugs of abuse and suggest that the stimulus and cognitive effects of benzodiazepine-receptor agonists are modulated by different brain mechanisms.