Orally delivered alprazolam, diazepam, and triazolam as reinforcers in rhesus monkeys

Benzodiazepines are among the most frequently prescribed drugs and are usually taken by mouth. However, there have been few studies of oral self-administration of these drugs, and the results of IV self-administration studies indicate that benzodiazepines are modest reinforcers. To determine if orally delivered alprazolam, diazepam, and triazolam could serve as reinforcers for rhesus monkeys, and to determine some of the conditions under which benzodiazepine reinforced behavior occurs. Diazepam or midazolam was initially established as a reinforcer by a fading procedure whereby increasing concentrations were added to a 1 or 2% ethanol solution, and subsequently the ethanol concentration was decreased in steps to zero. Diazepam- and midazolam-reinforced responding persisted in the absence of ethanol. Triazolam and alprazolam served as reinforcers when substituted for diazepam or midazolam. Alprazolam, diazepam, and triazolam served as effective reinforcers across a wide range of concentrations and under fixed-ratio sizes of 16 and 32. Rates of responding were usually far higher than that for the concurrently available vehicle, water. Drug intake (mg drug/kg body weight) generally increased with increases in drug concentration. When large drug amounts were consumed, signs of intoxication were observed. In contrast to reports of low response rates and weakly maintained behavior, the present results show that the three benzodiazepines can serve as effective reinforcers.