TY - JOUR T1 - Effects of fluoxetine and visual experience on glutamatergic and GABAergic synaptic proteins in adult rat visual cortex JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0126-15.2015 SP - ENEURO.0126-15.2015 AU - Simon Beshara AU - Brett R Beston AU - Joshua GA Pinto AU - Kathryn M Murphy Y1 - 2015/12/24 UR - http://www.eneuro.org/content/early/2015/12/24/ENEURO.0126-15.2015.abstract N2 - 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 SSRI affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a 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 pre- and post-synaptic 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.Significance Statement Patching therapy is the most common treatment for children with amblyopia. For many, the acuity recovered during patching is lost when the treatment stops leaving the child with persistent amblyopia. Fluoxetine has emerged as an interesting treatment option because it reinstates critical period-like ocular dominance plasticity and promotes acuity recovery in adult animals. It remains unclear, however, how this selective serotonin reuptake inhibitor affects visual cortex plasticity, which relies heavily on glutamatergic and GABAergic synapses. Here we report the effects of fluoxetine and visual manipulation on the visual cortex of adult rats. Surprisingly we found that fluoxetine did not reinstate a critical period-like state, but rather created a novel synaptic environment that favors mature NMDA and GABAA receptor subunits. ER -