title: Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus.
abstract: It has been proposed that antidepressants have neuroprotective effects on hippocampal neurons. To further test this hypothesis, brain-derived neurotrophic factor (BDNF), B cell lymphoma protein-2 (Bcl-2), and copper-zinc superoxide dismutase (Cu/Zn-SOD) were examined immunohistochemically in hippocampal neurons of Sprague-Dawley rats following daily treatment with 5 or 10 mg/kg of amitriptyline or venlafaxine for 21 days. At 5 mg/kg, both amitriptyline and venlafaxine increased the intensity of BDNF immunostaining in hippocampal pyramidal neurons, and the intensity of Bcl-2 immunostaining in hippocampal mossy fibers, but did not alter the Cu/Zn-SOD immunoreactivity. The high dose of venlafaxine, however, decreased the intensity of BDNF immunostaining in all subareas of the hippocampus and increased the intensity of Cu/Zn-SOD immunostaining in the dentate granular cell layer. The high dose of amitriptyline increased the intensity of Cu/Zn-SOD immunostaining, but did not affect the immunoreactivity of Bcl-2 or BDNF. These findings suggest that the chronic administration of amitriptyline or venlafaxine at 5 mg/kg, but not 10 mg/kg, may be neuroprotective to hippocampal neurons. These dose-related effects of antidepressant drugs on hippocampal neurons may have relevance to disparate findings in the field.
authors.affiliation: Neuropsychiatric Research Institute, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatooon, Canada.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Steven Richardson
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003511:Cyclohexanols / Q000494:pharmacology; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000639:Amitriptyline; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D003511:Cyclohexanols; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017367:Selective Serotonin Reuptake Inhibitors; D013482:Superoxide Dismutase; D000069470:Venlafaxine Hydrochloride