ABSTRACT
This study evaluated the effect of intermittent administration in the development of dependence to diazepam in chronic use of the drug. Gabapentin was used to provide an anxiolytic effect on drug-free days. During a 28-day treatment schedule, rats were given diazepam (15 mg/kg) once daily continuously, or intermittently with saline or gabapentin (50 mg/kg) on days 5, 10, 15, 20, and 25. Anxiety-like behavior was assessed on days 10 and 30 using the elevated plus-maze test and novelty-induced grooming test. Contrary to continuous administration, intermittent diazepam did not provide anxiolytic-like activity on day 10; instead, it prevented withdrawal anxiety on day 30. Gabapentin produced anxiolytic-like effects during the withdrawal period, but not on day 10. These results suggest that intermittent administration of diazepam (given either alone or alternatively with a drug possessing anxiolytic activity) may be of value in preventing the development of physical dependence during the chronic use of the drug. However, further studies are needed to demonstrate that this protocol could effectively produce anxiolytic activity on diazepam-free days.
Subject(s)
Anti-Anxiety Agents/adverse effects , Anti-Anxiety Agents/pharmacology , Anxiety/drug therapy , Diazepam/adverse effects , Diazepam/therapeutic use , Substance Withdrawal Syndrome/drug therapy , Amines/administration & dosage , Amines/pharmacology , Amines/therapeutic use , Animals , Anti-Anxiety Agents/administration & dosage , Anxiety/chemically induced , Cyclohexanecarboxylic Acids/administration & dosage , Cyclohexanecarboxylic Acids/pharmacology , Cyclohexanecarboxylic Acids/therapeutic use , Diazepam/administration & dosage , Diazepam/pharmacology , Disease Models, Animal , Drug Administration Schedule , Drug Interactions , Gabapentin , Grooming/drug effects , Male , Maze Learning/drug effects , Rats , Rats, Wistar , gamma-Aminobutyric Acid/administration & dosage , gamma-Aminobutyric Acid/pharmacology , gamma-Aminobutyric Acid/therapeutic useABSTRACT
The tricyclic amitriptyline and the selective serotonin reuptake inhibitor fluoxetine have distinct actions in animal models of anxiety, though both antidepressants are used against anxiety disorders. Grooming behavioural sequencing, rather than its general "activity" measures, has been suggested to measure effectively the pharmacologically induced anxiolytic and anxiogenic-like effects in rats and mice. In the present study, the acute effects of amitriptyline and fluoxetine on anxiety were re-evaluated by using an analysis algorithm in novelty-induced grooming activity in rats. Additionally, the effects on anxiety-like behaviour in the hole board were examined. Amitriptyline (5 and 10 mg/kg) and fluoxetine (5 and 10 mg/kg) not only affected the traditional gross measures, but also produced changes in incorrect transitions and regional distribution of grooming behaviour. High dose of fluoxetine showed an anxiogenic-like profile by reducing head dipping and rearing in the hole board. Depending on the effects on the behavioural microstructure of grooming activity, present findings imply that amitriptyline may possess anxiogenic and fluoxetine may possess anxiolytic activities. However, measures of hole board do not fully support this suggestion.
