title: Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress.
abstract: Background:Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), has been proposed to be more effective as an antidepressive drug as compared to other SSRIs. After chronic SSRI administration, the increase in synaptic levels of 5-HT leads to desensitization of somatodentritic 5-HT autoreceptors in the raphe nuclei. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors.Methods:Twenty four male rats were used in this study. Animals of CMS group were exposed to CMS. Animals of stressed and unstressed group were administrated with fluoxetine at dose of 1.0 mg/kg s well as 5.0 mg/kg repeatedly for 07 days 1 h before exposed to CMS. The objective of the present study was to evaluate that repeated treatment with fluoxetine could attenuate CMS-induced behavioral deficits.Results:Treatment with fluoxetine attenuated CMS-induced behavioral deficits. Fluoxetine administration induced hypophagia in unstressed as well as CMS rats. Acute and repeated administration of fluoxetine increased motor activity in familiar environment but only repeated administration increased exploratory activity in open field. Anxiolytic effects of fluoxetine were greater in unstressed rats. These anxiolytic effects were produced as result of repeated administration not on acute administration of fluoxetine at 1.0 mg/kg as well as 5.0 mg/kg.Conclusion:The present study demonstrated that CMS exposure resulted into behavioral deficits and produced depressive-like symptoms. Fluoxetine, an SSRI, administration attenuated behavioral deficits induced by CMS. Anxiolytic effects of repeated fluoxetine administration were greater in unstressed than CMS animals.
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Farhan
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: Darakshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
keywords: Chronic mild stress (CMS); Depression; Exploratory activity; Selective serotonin re-uptake inhibitors (SSRIs)