title: Regulation of c-Fos and NGF1-A by antidepressant treatments.
abstract: The influence of antidepressant treatments on the expression of c-Fos and NGF-1A, two immediate early gene (IEG) transcription factors, was examined. Administration of electroconvulsive seizures (ECS), tranylcypromine, or imipramine, three different classes of antidepressants, increased the expression of c-Fos mRNA and immunoreactivity in rat frontal cortex, but the magnitude of the increase for each treatment differed and the effect of imipramine was preceded by inhibition of c-Fos expression. Expression of NGF-1A was increased by acute or chronic administration of ECS or tranylcypromine, and by chronic (21 d), but not acute, administration of imipramine. To study the mechanisms underlying these differences, we examined the neurotransmitter receptors that regulate the expression of c-Fos. ECS- and tranylcypromine induction of c-Fos immunoreactivity in frontal cortex was partially inhibited by pretreatment with specific antagonists for alpha 1-adrenergic, beta-adrenergic, and 5-HT2A/2C, but not D2-dopamine receptors. ECS induction of c-Fos was also inhibited by D1-dopamine and NMDA glutamate receptor antagonists, suggesting that the greater induction of c-Fos by ECS results from activation of these, and possibly other, neurotransmitter receptors. In the hippocampus, antagonism of tranylcypromine was similar to that in frontal cortex, except the D1-dopamine receptor antagonist also blocked the c-Fos response. In contrast, antagonism of the ECS response in hippocampus was only blocked by the NMDA receptor antagonist. The results demonstrate that ECS- and tranylcypromine induction of c-Fos is mediated by activation of several different neurotransmitter receptors, but that the exact pharmacological profile is different for each treatment and brain region.
authors.affiliation: Department of Psychiatry and Pharmacology, Connecticut Mental Health Center, Yale University School of Medicine, New Haven 06508, USA.
authors.forename: S
authors.initials: S
authors.lastname: Morinobu
authors.forename: H
authors.initials: H
authors.lastname: Strausbaugh
authors.forename: R
authors.initials: R
authors.lastname: Terwilliger
authors.forename: R S
authors.initials: RS
authors.lastname: Duman
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D017781:Genes, Immediate-Early / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D017874:Immediate-Early Proteins; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D014191:Tranylcypromine / Q000494:pharmacology*
chemical_list: D018674:Adrenergic Antagonists; D000928:Antidepressive Agents; D001552:Benzazepines; D004268:DNA-Binding Proteins; D018492:Dopamine Antagonists; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D012702:Serotonin Antagonists; D014157:Transcription Factors; D014191:Tranylcypromine; D016291:Dizocilpine Maleate; D007650:Ketanserin; D011433:Propranolol; D006220:Haloperidol; D007099:Imipramine; D011224:Prazosin