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 extensively to study the behavioral effects and abuse potential of positive GABA(A) modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs 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 discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.
Gerak
L R
LR
Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Woolverton
W L
WL
Nader
M A
MA
Patrick
G A
GA
Harris
L S
LS
Winger
G
G
Woods
J H
JH
France
C P
CP
D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D005260:Female; D005445:Flunitrazepam / Q000009:adverse effects / Q000494:pharmacology*; D018757:GABA Modulators; D008253:Macaca mulatta; D008297:Male; D010424:Pentobarbital; D012054:Reinforcement, Psychology; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000517:prevention & control*; D019966:Substance-Related Disorders
D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D005445:Flunitrazepam; D010424:Pentobarbital