TY - JOUR
T1 - Comparison of the behavioral effects of bretazenil and flumazenil in triazolam-dependent and non-dependent baboons
AU - Weerts, Elise M.
AU - Ator, Nancy A.
AU - Kaminski, Barbara J.
AU - Griffiths, Roland R.
N1 - Funding Information:
The authors thank S. Womack, K. Ebaugh, and M. Cichocki for technical assistance in conducting these experiments and for performing many of the behavioral observations. Thanks also are due to Dr. D. Greenblatt for assistance with the analysis of blood samples. This research was supported by National Institute on Drug Abuse Grant R01 DA01147 (RRG). Manuscript preparation was supported by the National Institute on Drug Abuse Grant R01 DA14919 (EMW).
PY - 2005/9/5
Y1 - 2005/9/5
N2 - Behavioral effects of the benzodiazepine receptor partial agonist bretazenil were compared with those of the benzodiazepine receptor antagonist flumazenil under conditions in which three baboons received continuous intragastric (i.g.) infusion of vehicle and then continuous i.g. infusion of triazolam (1.0 mg/kg/day). In each condition, acute doses of flumazenil (0.01-3.2 mg/kg) and bretazenil (0.01-10.0 mg/kg) were administered every 2 weeks (beginning after 30 days of treatment in the triazolam-dependent condition). Food pellets were available during daily 20-h sessions. Following test injections, 60-min behavioral observations were conducted followed by a fine motor assessment. During chronic vehicle administration, neither drug produced changes in observed behaviors. Bretazenil increased pellets earned and time to complete the fine-motor task (10.0 mg/kg dose). During chronic triazolam dosing, both bretazenil and flumazenil precipitated benzodiazepine withdrawal syndromes, characterized by vomiting, tremors/jerks, and a decrease in pellets earned. Thus, bretazenil can function as an antagonist under conditions of benzodiazepine physical dependence.
AB - Behavioral effects of the benzodiazepine receptor partial agonist bretazenil were compared with those of the benzodiazepine receptor antagonist flumazenil under conditions in which three baboons received continuous intragastric (i.g.) infusion of vehicle and then continuous i.g. infusion of triazolam (1.0 mg/kg/day). In each condition, acute doses of flumazenil (0.01-3.2 mg/kg) and bretazenil (0.01-10.0 mg/kg) were administered every 2 weeks (beginning after 30 days of treatment in the triazolam-dependent condition). Food pellets were available during daily 20-h sessions. Following test injections, 60-min behavioral observations were conducted followed by a fine motor assessment. During chronic vehicle administration, neither drug produced changes in observed behaviors. Bretazenil increased pellets earned and time to complete the fine-motor task (10.0 mg/kg dose). During chronic triazolam dosing, both bretazenil and flumazenil precipitated benzodiazepine withdrawal syndromes, characterized by vomiting, tremors/jerks, and a decrease in pellets earned. Thus, bretazenil can function as an antagonist under conditions of benzodiazepine physical dependence.
KW - (Baboon)
KW - Benzodiazepine
KW - Bretazenil
KW - Flumazenil
KW - Physical dependence
KW - Precipitated withdrawal
KW - Triazolam
UR - http://www.scopus.com/inward/record.url?scp=27744571010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744571010&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.06.038
DO - 10.1016/j.ejphar.2005.06.038
M3 - Article
C2 - 16129429
AN - SCOPUS:27744571010
SN - 0014-2999
VL - 519
SP - 103
EP - 113
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-2
ER -