NEUROPHARMACOLOGY AND NEUROTOXICOLOGYAcute ketamine-induced neuroplasticity ribosomal protein S6 phosphorylation expression in drug addiction-related rat brain areasTedesco, Vincenzo; Ravagnani, Chiara; Bertoglio, Daniele; Chiamulera, CristianoAuthor Information Department of Public Health & Community Medicine, University of Verona, Verona, Italy Correspondence to Cristiano Chiamulera, PharmD, MSc, Department of Public Health & Community Medicine, Section Pharmacology, University of Verona, Policlinic G.B. Rossi, Piazzale Scuro 10, 37134, Verona, Italy Tel: +39 0458027277; fax: +39 0458027452; e-mail: [email protected] Received February 7, 2013 Accepted March 7, 2013 NeuroReport: May 8, 2013 - Volume 24 - Issue 7 - p 388-393 doi: 10.1097/WNR.0b013e32836131ad Buy Metrics Abstract Recent clinical studies show that a low dose of dissociative anesthetic ketamine (KET) induced a rapid antidepressant response that lasted for up to 7 days. This effect could be related to the capacity of KET to acutely induce molecular mechanisms of neuroplasticity engaged after chronic treatments. KET produces its actions by binding to the glutamate N-methyl-D-aspartic acid receptor, leading to increased activation of the mammalian target of rapamycin. Ribosomal protein S6 phosphorylation (rpS6P) is downstream to mammalian target of rapamycin and p70S6K activation, a molecular mechanism correlating synaptic protein synthesis and neuroplasticity. As neuroplasticity is also a key mechanism of addiction development, and considering the increasing abuse of KET, our aim was to examine the effect of acute KET administration on the expression of rpS6 in drug addiction-related cerebral areas. We tested in rats the effect of different KET doses (5 or 10 mg/kg, intraperitoneally) on rpS6P expression by immunolocalization in prelimbic (PRL) and infralimbic (IL) cortices, nucleus accumbens core (NAcC) and nucleus accumbens shell (NAcS), hippocampus (CA1 and CA3), and basolateral amygdala (BLA). Expression levels of rpS6 were quantified. A significant dose-related increase in rpS6P expression in PRL, IL, BLA, NAcC but not in the NAcS and hippocampus was found after acute KET. These data confirm acute KET-induced neuroplasticity effects, and extend these findings to drug addiction-related brain areas. © 2013 Lippincott Williams & Wilkins, Inc.