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.

Neural Activation by Milnacipran and Memory Extinction

“…Chronic treatment with imipramine, desipramine and sertraline down-regulated stress-induced expression in c-Fos mRNA in the frontal cortex [19]. In the present study, repeated administration of milnacipran reduced Fos counts in the infralimbic region.…”

Induction of c-Fos and ΔFosB Immunoreactivity in Rat Brain by Vagal Nerve Stimulation

“…In general, increases have not been reported in the hippocampus and many other regions of brain and effects in cortical areas have been quite inconsistent. Acute electroconvulsive shock (ECS) also increases c-Fos in cortex and hippocampus (Cole et al, 1990;Hope et al, 1994;Morinobu et al, 1997;Winston et al, 1990). Interestingly, chronic treatment of rats with either paroxetine (Muigg et al, 2007) or citalopram (Kuipers et al, 2006) does not increase c-Fos in any brain region examined, including the CeA.…”

Comparison of Alterations in c-fos and Egr-1 (zif268) Expression Throughout the Rat Brain Following Acute Administration of Different Classes of Antidepressant Compounds

“…injection of vehicle or psychoactive drug (n ¼ 6 per group). Drugs and doses included LiCl (a mood stabilizer; 75 mg/kg), mirtazapine (a noradrenaline and serotonin-selective antidepressant; 2 mg/kg), fluoxetine (a selective serotonin (5-HT) reuptake inhibitor (SSRI), 5 mg/kg), or imipramine (a tricyclic antidepressant (TCA) inhibits NA and 5-HT reuptake; 15 mg/kg) based on previous c-fos experiments (Lamprecht and Dudai, 1995;Morinobu et al, 1997;Torres et al, 1998). The exception was mirtazapine, for which there were no previous IEG studies and this dose was selected on behaviorally active doses in male rats (de Boer, 1996).…”