NDLI: In vivo Effect of Antidepressants on [$^{3}$H]paroxetine Binding to Serotonin Transporters in Rat Brain

Content Provider	Springer Nature Link
Author	Nadgir, Subhash M. Malviya, Manish
Copyright Year	2008
Abstract	Amine transporters are major target for development of various pharmacological agents to treat behavioral disorders. Serotonin transporters (SERT) have been implicated in the etiology of depression and drugs acting on SERT can be effective in treating depression. The aim of the present study was to study the in vivo effect of various antidepressants on [$^{3}$H]paroxetine binding to SERT in regions of rat brain. Rats were treated with tricyclic antidepressant (TCAs) such as amitriptyline (AMI), serotonin/norepinephrine reuptake inhibitor (SNRIs) such as clomipramine (CMI), and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (FLX) and citalopram (CIT) (10 mg/kg body wt.) for 30 days. Density of SERT was measured in cortex and hippocampus using [$^{3}$H]paroxetine (0.03–1.0 nM) in presence and absence of 10 μM fluoxetine as displacer. It was observed that the density of cortical SERT was significantly decreased with CMI (68%, P < 0.0001), FLX (67%, P < 0.0001), CIT (54%, P < 0.0001), and AMI (52%, P < 0.0001) treatment, when compared to the density of 120.7 ± 4.0 fmol/mg protein in control rats, without altering the affinity (Kd) of [$^{3}$H]paroxetine to the transporters. The density of SERT in hippocampus was also significantly decreased with FLX (65%, P < 0.0001), CMI (54%, P < 0.0001), CIT (52%, P < 0.0001) and AMI (46%, P < 0.0001) treatment, when compared to the density of 74.0 ± 2.6 fmol/mg protein in control rats, without altering the affinity of [$^{3}$H]paroxetine to the transporters. Displacement study showed high affinity for CMI > CIT > FLX. The results suggest that chronic antidepressant treatment significantly down-regulates both cortical and hippocampal SERT in rat brain and SSRIs have high affinity for SERT than TCAs.
Starting Page	2250
Ending Page	2256
Page Count	7
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	33
Issue Number	11
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2008-04-25
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Antidepressants [$^{3}$H]paroxetine [$^{3}$H]imipramine Serotonin transporters (SERT) Radioligand binding Rat brain In vivo Neurology Biochemistry Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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