Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex

eNeuro. 2016 Jan 4;2(6):ENEURO.0126-15.2015. doi: 10.1523/ENEURO.0126-15.2015. eCollection Nov-Dec 2015.


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.

Keywords: adult plasticity; amblyopia; fluoxetine; monocular deprivation; receptors; visual cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dominance, Ocular / drug effects
  • Evoked Potentials, Visual / drug effects*
  • Fluoxetine / pharmacology
  • GABAergic Neurons / drug effects*
  • Male
  • Neuronal Plasticity / drug effects*
  • Rats, Long-Evans
  • Serotonin Uptake Inhibitors / pharmacology*
  • Synapses / drug effects*
  • Visual Cortex / drug effects*


  • Serotonin Uptake Inhibitors
  • Fluoxetine