title: Effects of nerve growth factor (NGF), fluoxetine, and amitriptyline on gene expression profiles in rat brain.
abstract: Evidence suggests that nerve growth factor (NGF) may have antidepressant properties but the pharmacological mechanisms remain unknown. Previously, we found that NGF improved performance in the forced swim test in Flinders Sensitive Line rats, but did not appear to have similar biochemical actions with the antidepressant fluoxetine. Gene expression profiles for neurotransmitter receptors and regulator-related genes in the amygdala/hippocampus were determined in rats treated for 14days with NGF, fluoxetine, amitriptyline, or saline. Gene expression was measured using an RT(2) profiler PCR Array System to determine the basis for this effect. Compared with saline, there were numerous genes with significantly altered mRNA levels in the amygdala/hippocampal region. Overlap was found between the mRNA levels of genes altered by NGF and the two antidepressant medications including genes related to the cholinergic and dopaminergic systems. However, decreased mRNA levels of Drd5, Sstr3, Htr3a, and Cckar genes in the amygdala/hippocampus were uniquely regulated by NGF. The results of this study are consistent with a previous conclusion that the antidepressant effects of NGF are mediated through non-traditional receptors for traditionally considered neurotransmitters and may suggest a particular utility of NGF in treating comorbid depression and addiction.
authors.affiliation: Providence Veterans Affairs Medical Center, Brown University, RI 02912, USA. john_mcgeary@brown.edu
authors.forename: John E
authors.initials: JE
authors.lastname: McGeary
authors.forename: Volkan
authors.initials: V
authors.lastname: Gurel
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Knopik
authors.forename: James
authors.initials: J
authors.lastname: Spaulding
authors.forename: John
authors.initials: J
authors.lastname: McMichael
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; C493607:Drd5 protein, rat; D043886:Receptor, Cholecystokinin A; D044406:Receptors, Serotonin, 5-HT3; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; D005473:Fluoxetine; D050641:Receptors, Dopamine D5; D000639:Amitriptyline; D020932:Nerve Growth Factor