title: Effect of antidepressant drugs on the vmPFC-limbic circuitry.
abstract: Our recent study indicates that the lesions of the prefrontal cortex in rats result in depressive-like behavior in forced swim test and REM sleep alterations, two well-established biomarkers of depression disorder. We hypothesized that antidepressants may target the PFC to reverse depression. Systemic injections of antidepressants: the tricyclic antidepressant desipramine (DMI), the selective serotonin reuptake inhibitor fluoxetine, and the NMDA-antagonist ketamine selectively increased cFos expression (a marker of neuronal activity) in the deep layers of the ventromedial PFC (vmPFC) in rats. Of the vmPFC's limbic system targets, only the nucleus accumbens (NAc) was also activated by DMI. Using a retrograde tracer and a neuronal toxin, we also found that DMI-activated vmPFC neurons project to the NAc and that NAc activation by DMI was lost following vmPFC lesion. These results suggest that the vmPFC may be an essential target of antidepressant drugs, its projections to the NAc may be a key circuit regulating antidepressant action, and dysfunction of this pathway may contribute to depression.
authors: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors: Celene H
authors: CH
authors: Chang
authors: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors: Michael C
authors: MC
authors: Chen
authors: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA. Electronic address: jlu@bidmc.harvard.edu.
authors: Jun
authors: J
authors: Lu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications; D002452:Cell Count; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D005786:Gene Expression Regulation / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D016760:Proto-Oncogene Proteins c-fos; D003891:Desipramine
keywords: Depression; Desipramine; Fluoxetine; Ketamine; Nucleus accumbens; cFos
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