title: Acute ketamine-induced neuroplasticity: ribosomal protein S6 phosphorylation expression in drug addiction-related rat brain areas.
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.
authors.affiliation: Department of Public Health & Community Medicine, University of Verona, 37134 Verona, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tedesco
authors.forename: Chiara
authors.initials: C
authors.lastname: Ravagnani
authors.forename: Daniele
authors.initials: D
authors.lastname: Bertoglio
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiamulera
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D038601:Ribosomal Protein S6 / Q000187:drug effects* / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects
chemical_list: D000778:Anesthetics, Dissociative; D016194:Receptors, N-Methyl-D-Aspartate; D038601:Ribosomal Protein S6; D007649:Ketamine; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases