Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.
The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans.
Bourin
M
M
GIS Medicament, Faculty of Medicine, Nantes University, France.
Hascoet
M
M
Mansouri
B
B
Colombel
M C
MC
Bradwejn
J
J
D000525:Alprazolam / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001960:Bromazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004597:Electroshock; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D010919:Placebos; D012890:Sleep / Q000187:drug effects
D010919:Placebos; D001569:Benzodiazepines; D008140:Lorazepam; D001960:Bromazepam; D000525:Alprazolam