PMID- 12496940 OWN - NLM STAT- MEDLINE DCOM- 20030317 LR - 20221207 IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 28 IP - 1 DP - 2003 Jan TI - Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus. PG - 53-62 AB - 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. FAU - Xu, Haiyun AU - Xu H AD - Neuropsychiatric Research Institute, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatooon, Canada. FAU - Steven Richardson, J AU - Steven Richardson J FAU - Li, Xin-Min AU - Li XM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Antidepressive Agents) RN - 0 (Antidepressive Agents, Tricyclic) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclohexanols) RN - 0 (Neuroprotective Agents) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Serotonin Uptake Inhibitors) RN - 1806D8D52K (Amitriptyline) RN - 7D7RX5A8MO (Venlafaxine Hydrochloride) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Amitriptyline/pharmacology MH - Animals MH - Antidepressive Agents/*pharmacology MH - Antidepressive Agents, Tricyclic/pharmacology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cyclohexanols/pharmacology MH - Densitometry MH - Dose-Response Relationship, Drug MH - Hippocampus/drug effects/enzymology/*metabolism MH - Immunohistochemistry MH - Male MH - Neuroprotective Agents/*metabolism MH - Proto-Oncogene Proteins c-bcl-2/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Selective Serotonin Reuptake Inhibitors/pharmacology MH - Superoxide Dismutase/*metabolism MH - Venlafaxine Hydrochloride MH - Weight Gain/drug effects EDAT- 2002/12/24 04:00 MHDA- 2003/03/18 04:00 CRDT- 2002/12/24 04:00 PHST- 2002/12/24 04:00 [pubmed] PHST- 2003/03/18 04:00 [medline] PHST- 2002/12/24 04:00 [entrez] AID - 1300009 [pii] AID - 10.1038/sj.npp.1300009 [doi] PST - ppublish SO - Neuropsychopharmacology. 2003 Jan;28(1):53-62. doi: 10.1038/sj.npp.1300009.