The novel monoamine reuptake inhibitor and potential antidepressant, S33005, induces Arc gene expression in cerebral cortex

• Published in: European journal of pharmacology 2004-04, Vol.489 (3), p.179-185
• Main Authors: Pei, Qi, Sprakes, Marie, Millan, Mark J, Rochat, Catherine, Sharp, Trevor
• Format: Article
• Language: English
• Subjects: 5-hydroxytryptamine; Animals; Antidepressant; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacokinetics; Arc (activity-regulated cytoskeletal associated protein); Biological and medical sciences; Brain-Derived Neurotrophic Factor - chemistry; Brain-Derived Neurotrophic Factor - physiology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Cerebral Cortex - ultrastructure; Cyclohexanols - administration & dosage; Cyclohexanols - pharmacokinetics; Cytoskeletal Proteins; Drug Administration Schedule; Gene Expression - genetics; Immediate-Early Proteins - genetics; Injections, Intraperitoneal; Male; Medical sciences; Nerve Tissue Proteins - genetics; Neuroplasticity; Neurotransmitter Uptake Inhibitors - administration & dosage; Neurotransmitter Uptake Inhibitors - pharmacokinetics; Pharmacology. Drug treatments; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Pyramidal Cells - ultrastructure; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; SNRI (selective 5-HT/noradrenaline reuptake inhibitor); Time Factors; Venlafaxine Hydrochloride
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.03.002

Recent data show that corticolimbic expression of the effector immediate early gene Arc is up-regulated by standard antidepressant drugs. Here, we tested the effect upon Arc expression of a novel antidepressant and selective 5-hydroxytryptamine/noradrenaline reuptake inhibitor (SNRI), (−)1-(1-dimethylaminomethyl) 5-methoxybenzocyclobutan-1-yl) cyclohexanol (S33005). Arc mRNA abundance in frontal, cingulate, orbital and parietal cortices, hippocampus (CA1 pyramidal layer) and striatum was elevated in rats treated daily for 14 but not 7 days with 10 mg/kg i.p. S33005 compared to saline. Fourteen but not 7 days treatment with 10 mg/kg i.p. venlafaxine, the prototypical SNRI, also elevated Arc mRNA, but its effects were not as pronounced and detected in fewer regions, compared to S33005. Neither S33005 nor venlafaxine altered Arc mRNA after acute injection nor altered brain derived neurotrophic factor mRNA after repeated administration. These data demonstrate that sustained treatment with SNRIs increases Arc expression in corticolimbic regions, and underpin previous neurochemical and behavioural evidence that S33005 is efficacious in models predictive of antidepressant action.