The novel monoamine reuptake inhibitor and potential antidepressant, S33005, induces Arc gene expression in cerebral cortex.
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.
Pei
Qi
Q
Department of Pharmacology, Oxford University, Mansfield Road, Oxford OX1 3QT, UK.
Sprakes
Marie
M
Millan
Mark J
MJ
Rochat
Catherine
C
Sharp
Trevor
T
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D003511:Cyclohexanols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003598:Cytoskeletal Proteins; D004334:Drug Administration Schedule; D015870:Gene Expression / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics*; D007274:Injections, Intraperitoneal; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
C432168:1-(1-dimethylaminomethyl-5-methoxybenzocyclobutan-1-yl)cyclohexanol; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D003511:Cyclohexanols; D003598:Cytoskeletal Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D000069470:Venlafaxine Hydrochloride