title: Chronic fluoxetine treatment has a larger effect on the density of a serotonin transporter in the Flinders Sensitive Line (FSL) rat model of depression than in normal rats.
abstract: The 5-hydroxytryptamine system is thought to play a crucial role in the pathophysiology of depression and represents the target for selective 5-HT reuptake inhibitors (SSRIs). Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were bred from Sprague-Dawley (SPD) rats to produce strains with increased (FSL) or decreased (FRL) sensitivity to the cholinesterase inhibitor. The FSL rats have been identified as a good model of depression. Many studies in normal rats showed that chronic treatments with SSRIs reduce the densities of SERT. The objective of the present investigation was to assess the influence of chronic fluoxetine treatment on SERT density (Bmax; fmol/mg) in the FSL rat model of depression, relative to that in the FRL rats and SPD rats. FSL, FRL and SPD rats were randomly assigned into groups receiving the vehicle or 10 mg/kg of fluoxetine i.p. for 14 days. Binding was assessed by incubating the brain sections in a buffer containing 20 pM of [(125)I]-RTI-55 [[(125)I](-)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane and 200 nM of GBR12935 [1-(2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine]. The fluoxetine treatment reduced B(max) in all three rat strains when the saline and respective fluoxetine groups were compared (e.g., the FSL-SAL relative to FSL-FLX groups). Chronic fluoxetine treatment reduces the densities of SERT in the FSL rats to a larger extent than in the normal SPD control rats.
authors.affiliation: Department for Neurology and Neurosurgery, Cone Neurosurgical Research Laboratory and Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Kovacević
authors.forename: Ivan
authors.initials: I
authors.lastname: Skelin
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D000928:Antidepressive Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine