The increase of excitatory postsynaptic current (EPSC) response and spine head diameter sustained for up to 1 week after the Ket-10 or Ket-1/Li-10 combination treatment. Rats were administered saline, Ket-10, or Ket-1/Li-10 and 1 week later whole-cell recordings were conducted in slices and post-hoc two-photon microscopy sampled and analyzed. (a) Representative traces showing EPSCs recorded from mPFC layer V pyramidal neuron from rats treated under the described treatment conditions. (b) Frequency of 5-hydroxytryptamine (5-HT)- and hcrt-induced EPSCs. Results are the mean±SEM percent of vehicle control (F=5.39 for 5-HT and F=4.93 for hcrt, p<0,05; post-hoc test *p<0.05 vs control, **p<0.01 vs control; n=13–22 cells from 4–7 rats). (c) Two-photon images of apical tuft branch segments from recorded mPFC layer V pyramidal neurons filled with neurobiotin and post-hoc staining with streptavidin conjugated to Alexa 594. Scale bar shown in left panel. (d) Summary of data (n=11–12 cells) showing the spine number (top) and spine head diameter (bottom). (F=0.8 for spine density, p=0.44; F=15.68 for spine head diameter, p<0.05, post-hoc test **p<0.01 vs control).