Antidepressant drug treatment induces Arc gene expression in the rat brain.
The mechanism underlying the therapeutic effect of antidepressants is not known but neuroadaptive processes akin to long-term potentiation have been postulated. Arc (Activity-regulated, cytoskeletal-associated protein) is an effector immediate early gene implicated in LTP and other forms of neuroplasticity. Recent data show that Arc expression is regulated by brain 5-hydroxytryptamine neurones, a target of many antidepressants. Here in situ hybridisation and immunohistochemistry were used to examine whether Arc expression in rat brain is altered by antidepressant drug treatment. Repeated administration of the monoamine reuptake inhibitors paroxetine, venlafaxine or desipramine induced region-specific increases in Arc mRNA. These increases were greatest in regions of the cortex (frontal and parietal cortex) and hippocampus (CA1 layer) and absent in the caudate putamen. Repeated treatment with the monoamine oxidase inhibitor, tranylcypromine, increased Arc mRNA in a similar fashion to the monoamine reuptake inhibitors. The antidepressant drugs also increased the number of Arc-immunoreactive cells in the parietal cortex. Acute antidepressant injection, and repeated administration of the antipsychotic drug chlorpromazine, produced either limited or no changes in Arc mRNA. The data suggest that chronic treatment with antidepressant drugs induces Arc gene expression in specific regions across the rat forebrain. Up-regulation of Arc expression may be part of the process by which antidepressant drugs achieve long-term changes in synaptic function in the brain.
University Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, UK. qi.pei@pharm.ox.ac.uk
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Zetterström
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D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003891:Desipramine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D017374:Paroxetine / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014191:Tranylcypromine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D002746:Chlorpromazine; D003511:Cyclohexanols; D003598:Cytoskeletal Proteins; D003891:Desipramine; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors; D014191:Tranylcypromine; D000069470:Venlafaxine Hydrochloride; C092069:activity regulated cytoskeletal-associated protein