title: Molecular adaptation to chronic antidepressant treatment: evidence for a more rapid response to the novel α₂-adrenoceptor antagonist/5-HT-noradrenaline reuptake inhibitor (SNRI), S35966, compared to the SNRI, venlafaxine.
abstract: Evidence of early changes in neural plasticity may aid the prediction of rapid-onset antidepressant drugs. Here we compared the dual α₂-adrenoceptor antagonist/5-HT-noradrenaline reuptake inhibitor (SNRI), S35966, to the SNRI, venlafaxine, with regards to their effect on rat brain expression of a panel of neural plasticity-related genes: Arc, BDNF, and VGLUT1, as well as Homer1a and Shank1B (not studied previously). Abundance of mRNA was determined by in-situ hybridization in cortical and hippocampal regions 2 h and 16 h following drug administration for 14, 7 and 1 d. After 14 d, both S35966 and venlafaxine increased mRNA of all genes, including Homer1a and Shank1B, and effects were similarly time- and region-dependent. After 7 d, S35966 elevated Arc, Shank1B and BDNF mRNA, whereas venlafaxine increased Shank1B mRNA only. Finally, after 1 d (acute administration), S35966 increased Arc and Homer1a mRNA whereas venlafaxine had no effect on any gene examined. In summary, a 14-d course of treatment with S35966 or venlafaxine induced similar region- and time-dependent increases in expression of neural plasticity-related genes including Shank1B and Homer1a. Some genes responded earlier to S35966, suggesting that drugs with combined α₂-adrenoceptor antagonist/SNRI properties may elicit more rapid changes in markers of neural plasticity than a SNRI alone.
authors: University Department of Pharmacology, Oxford, UK. florence.serres@pharm.ox.ac.uk
authors: Florence
authors: F
authors: Serres
authors: Mark J
authors: MJ
authors: Millan
authors: Trevor
authors: T
authors: Sharp
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012701:Serotonin; D000069470:Venlafaxine Hydrochloride; D009638:Norepinephrine