ABSTRACT
In the present study we have monitored effects of repeated coadministration of fluoxetine with midazolam; a benzodiazepine (CNS depressant). It is the primary drug of choice for procedural sedation, preoperative sedation, and in emergency departments. Repeated administration of this drug is reported to have abuse potential and may cause this by increasing dopaminergic neurotransmission. Since an important role of serotonin is there in the pathophysiology of anxiety and addiction, administration of midazolam may involve altered 5-HT metabolism as well. Present study was designed to monitor effects of repeated administration of fluoxetine with midazolam. Effects of fluoxetine and midazolam coadministration were monitored on motor activities in familiar and novel environments, hot plate test, forced swim test, conditioned place preference test and levels of dopamine, 5-HT and their metabolites. Both midazolam (2.5mg/kg) and fluoxetine (1mg/kg) were administered orally for 12 days. Conditioned place preference test was performed on day 13. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study show attenuation of midazolam-induced reinforcement upon repeated co-administration of fluoxetine. These could be implicated to increased therapeutic utility of midazolam and related benzodiazepines.
Subject(s)
Fluoxetine/pharmacology , Fluoxetine/pharmacokinetics , Midazolam/pharmacology , Midazolam/pharmacokinetics , Animals , Behavior, Animal/drug effects , Drug Interactions , Hypnotics and Sedatives/pharmacokinetics , Hypnotics and Sedatives/pharmacology , Male , Motor Activity , Random Allocation , Rats , Rats, Wistar , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Selective Serotonin Reuptake Inhibitors/pharmacology , Substance-Related DisordersABSTRACT
Present study was designed to monitor the dose dependent effects of lorazepam; a benzodiazepine (CNS depressant). It is the primary drug of choice for treatment of anxiety and to produce calming effects. However, repeated administration of this lorazepam causes dependence and this might be caused by increased dopaminergic neurotransmission. Besides dopamine, 5-hydroxy tryptamine (5-HT) has also been reported to have pivotal role in the pathophysiology as well as treatment of anxiety and addiction. Repeated administration of lorazepam might involve altered 5-HT metabolism as well. Present study was therefore designed to monitor dose-dependent effects of lorazepam and to select its optimum dose for further experiments and pharmacological interventions. Effects of lorazepam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, forced swim test and metabolism of dopamine and 5-HT. oral administration of lorazepam was done at the doses of 0mg/kg, 2mg/kg, 4mg/kg and 6mg/kg. Behaviors parameters were monitored following single administration of lorazepam. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of lorazepam and related benzodiazepines.
Subject(s)
Anti-Anxiety Agents/administration & dosage , Brain/drug effects , Brain/metabolism , Lorazepam/administration & dosage , Motor Activity/drug effects , Animals , Dopamine/metabolism , Eating/drug effects , Eating/physiology , Eating/psychology , Exploratory Behavior/drug effects , Exploratory Behavior/physiology , Male , Motor Activity/physiology , Rats , Rats, Wistar , Serotonin/metabolismABSTRACT
In the present study we have monitored dose dependent effects of midazolam; a benzodiazepine (CNS depressant). It is the primary drug of choice for procedural sedation, preoperative sedation, and in emergency departments. Repeated administration of this drug is reported to have abuse potential and may cause this by increasing dopaminergic neurotransmission. Since an important role of 5-hydroxy tryptamine (5-HT) is there in the pathophysiology of anxiety and addiction, administration of midazolam may involve altered 5-HT metabolism as well. Present study was designed to monitor dose-dependent effects of midazolam and select the optimum dose for further experiments. Effects of midazolam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, hot plate test, forced swim test and levels of dopamine, 5-HT and their metabolites. Midazolam was administered orally (0mg/kg, 2.5mg/kg, 5.0mg/kg and 10mg/kg) and behaviors were monitored post single midazolam administrations. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of midazolam and related benzodiazepines.
