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Individuals who are moderate drinkers are at increased risk to abuse alcohol. Moreover, women are more vulnerable than men to the adverse consequences of alcohol consumption and recent data indicate that the drinking pattern in women is becoming more similar to that of men. However, few studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of alcohol, compared to female light drinkers (LD). Fifteen female MD who consumed an average of 34.7 drinks/month were compared to 15 female LD who consumed an average of 6.7 drinks/month. None of the participants had a first-degree family history of alcoholism or substance abuse. The acute effects of alcohol (0, 0.25, 0.50, 0.75 mg/kg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures, subjective-effects questionnaires and observer ratings. Alcohol impaired performance in a dose-related manner on all performance tasks for both groups of females. However, MD were less impaired than LD on balance and Digit Symbol Substitution Test (DSST). This reduced response was also evident from the observer ratings, with MD being viewed as less impaired by alcohol than LD. While ratings of Drug Liking increased in both groups of women on the ascending limb of the breath alcohol curve, alcohol was disliked by LD on the descending limb and LD reported increased ratings of Bad Drug Effects following the high dose of alcohol. The reduced performance impairment, coupled with the positive subjective effects and relative absence of adverse subjective effects, suggestive of behavioral tolerance, could result in a progression towards increased alcohol consumption among moderate female social drinkers.

DN-2327 (pazinaclone) is a new non-benzodiazepine compound which has high affinity for benzodiazepine receptors. The acute behavioral effects and abuse liability of DN-2327 (2, 4 and 8mg) were compared to those of the benzodiazepine anxiolytic alprazolam (0.25, 0.5 and 1mg) in ten normal adult male volunteers using a double-blind, placebo-controlled, outpatient design. For both drugs, the neck effect occurred approximately 1.5h after drug administration. Both drugs also produced comparable dose-related effects on several measures related to sedation, as well as on subject- and observer-rated strength of drug effect. Both alprazolam and DN-2327 produced dose-related impairments on various performance measures; on some tasks, the impairment was greater for DN-2327. In contrast, there were no differences between DN-2327 and alprazolam on observer-rated measures. Although no measures of drug-taking were made in this study, to the extent that self-reported effects predict reinforcing effects, the data suggest little liability for abuse of the two compounds in this subject population. Ratings of 'drug liking' and 'willing to take the drug again' were not increased following alprazolam. Although DN-2327 did not increase ratings of 'willing to take the drug again', DN-2327 did produce small but significant increases on ratings of 'drug liking'. Overall, these results suggest that the non-benzodiazepine DN-2327 has a pharmacological profile that is similar to that of benzodiazepines.

Two groups of pigeons were trained to discriminate a histamine H(1)-antagonist (chlorpheniramine or promethazine) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. There was no cross-substitution with these two histamine H(1)-antagonists: that is, promethazine failed to substitute reliably for chlorpheniramine in chlorpheniramine-trained pigeons, and chlorpheniramine failed to substitute reliably for promethazine in promethazine-trained pigeons. Among the other histamine H(1)-antagonists tested, tripelennamine consistently produced greater than 80% responding in chlorpheniramine-trained pigeons but not in promethazine-trained pigeons. In contrast, diphenhydramine consistently produced greater than 80% responding in promethazine-trained pigeons but not in chlorpheniramine-trained pigeons. Similarly, chlorcyclizine partially substituted for promethazine and failed to substitute for chlorpheniramine. d-Amphetamine substituted for chlorpheniramine in 2 of 4 pigeons and partially in a third pigeon, whereas d-amphetamine substituted for promethazine in only 1 of 4 pigeons. Pentobarbital failed to produce greater than 80% responding in either chlorpheniramine- or promethazine-trained pigeons. The results of the present study demonstrate that the histamine H(1)-antagonists, chlorpheniramine and promethazine, have differential discriminative stimulus effects in pigeons. These findings suggest that the discriminative stimulus effects of this class of compounds are not based entirely on their ability to act as antagonists at histamine H(1)-receptors.