Behavioral effects of flunitrazepam: reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats

Flunitrazepam was evaluated in several procedures that have been used exten sively to study the behavioral effects and abuse potential of positive GABA (A) modulators. One group of monkeys (n = 3) responded to receive injection s of methohexital or saline (i.v.) while other groups (n = 2-4/group) discr iminated vehicle from tither pentobarbital or triazolam. Other monkeys (n = 2) received diazepam daily and discriminated flumazenil from vehicle. Fina lly, the ability of flunitrazepam to prevent the emergence of withdrawal si gns in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i .v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimina tion studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute fur flumazenil. In rats (n = 3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobar bital treatment: withdrawal signs emerged when either pentobarbital or flun itrazepam treatment was terminated. Taken together with data from previous studies. these data suggest that the abuse liability of flunitrazepam is co mparable to that of other benzodiazepines. (C) 2001 Elsevier Science Irelan d Ltd. All rights reserved.