The effects of antidepressant drug treatments on activator protein-1 binding activity in the rat brain

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2002-02, Vol.26 (2), p.375-381
• Main Authors: Tamura, Tatsuji, Morinobu, Shigeru, Okamoto, Yasumasa, Kagaya, Ariyuki, Yamawaki, Shigeto
• Format: Article
• Language: English
• Subjects: Activator protein-1; Animals; Antidepressive Agents - administration & dosage; Antidepressive Agents - metabolism; Antidepressive Agents - pharmacology; Binding, Competitive - drug effects; Binding, Competitive - physiology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Dose-Response Relationship, Drug; Imipramine; Injections, Intraperitoneal; Lithium; Lithium - administration & dosage; Lithium - metabolism; Lithium - pharmacology; Male; Medical sciences; Neuropharmacology; Paroxetine; Pharmacology. Drug treatments; Protein Binding - drug effects; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Restraint stress; Restraint, Physical; Stress, Physiological - drug therapy; Stress, Physiological - metabolism; Transcription Factor AP-1 - metabolism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/S0278-5846(01)00286-X

Since a long-term administration of antidepressant drugs and mood stabilizers is required in the treatment of mood disorders, the regulation of gene expression by these drugs that is mediated by transcription factors, such as activator protein-1 (AP-1) complex, may play an important role in the therapeutic action. In this study, the authors investigated the influence of lithium, antidepressant drugs and stress on AP-1 binding activity in the rat brain. In addition, we examined pretreatment with these drugs on the expression of AP-1 binding activity in response to stress. A gel shift assay was used to measure the levels of AP-1 binding activity. Our results indicate that neither acute nor chronic treatment with antidepressant drugs affects in AP-1 binding activity in the rat frontal cortex or hippocampus. However, the authors found that acute restraint stress for 90 min upregulated the induction of AP-1 binding activity in the rat frontal cortex. In addition, chronic pretreatment with imipramine, but not lithium or paroxetine, downregulated the induction of AP-1 binding activity in response to acute restraint stress in the frontal cortex. The functional classification of antidepressant drugs based on the downregulation of restraint stress-induced AP-1 binding activity may contribute to the advances in our understanding of the pathogenesis of depression.