title: Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex.
abstract: Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity.
authors.affiliation: McMaster Integrative Neuroscience Discovery and Study (MiNDS) Program, McMaster University , Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Beshara
authors.affiliation: McMaster Integrative Neuroscience Discovery and Study (MiNDS) Program, McMaster University, Hamilton, Ontario L8S 4K1, Canada; Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Ontario L8S 4K1, Canada; Department of Psychology, University of Toronto Mississauga, Mississauga, L5L 1C6, ON.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Beston
authors.affiliation: McMaster Integrative Neuroscience Discovery and Study (MiNDS) Program, McMaster University, Hamilton, Ontario L8S 4K1, Canada; Health Care Investment Banking, Credit Suisse AG, San Francisco, CA 94108.
authors.forename: Joshua G A
authors.initials: JG
authors.lastname: Pinto
authors.affiliation: McMaster Integrative Neuroscience Discovery and Study (MiNDS) Program, McMaster University, Hamilton, Ontario L8S 4K1, Canada; Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D023882:Dominance, Ocular / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D020318:Rats, Long-Evans; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*; D014793:Visual Cortex / Q000187:drug effects*
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: adult plasticity; amblyopia; fluoxetine; monocular deprivation; receptors; visual cortex