Procedures and criteria for the Retest day were identical to those on the initial Response Discrimination day. On the following day, mice were then trained to always enter the arm that contained the visual cue, the location of which was again pseudorandomly varied in the left and right arms. Training was continued until a mouse made a correct choice on the probe trial. For each day, we analyzed the total number of trials to criterion and the number of probe trials required to reach criterion. For the Shift to Visual-Cue Learning day, errors were scored as entries into arms that did not contain the visual cue, and they were further broken down into three subcategories to determine whether CIE altered the ability to either shift from the previously learned strategy or to maintain the new strategy after perseveration had ceased. In order to detect shifts in the strategies that animals used, trials were separated into consecutive blocks of four trials each. A perseverative error occurred when a mouse made the same egocentric response as required during the Response Discrimination day, but which was opposite to the direction of the arm containing the visual cue. Six of every 12 consecutive trials required the mouse to respond in this manner. A perseverative error was scored when the mouse entered the incorrect arm on three or more trials per block of 4 trials. Once the mouse made less than three perseverative errors in a block, all subsequent errors were now scored as regressive errors. The third type of error, termed “never reinforced” errors, was scored when a mouse entered the incorrect arm on trials where the visual cue was placed on the same side that the mouse had been trained to enter on the previous day. Current strategies for NGF therapy in AD use highly invasive approaches, such as a neurosurgical intracerebroventricular injection of NGF or a parenchimal injection of cells secreting hNGF or of viruses harboring hNGF gene. To fully exploit the therapeutic potential of NGF in a noninvasive manner, its therapeutic window must be improved, by increasing the brain distribution, while limiting NGF paininducing actions. The intranasal delivery represents a viable option to non invasively increase NGF biodistribution in the brain, where it exerts anti-neurodegenerative actions. NGF intranasal delivery minimizes the build-up of peripheral NGF concentration, even if residual leakage and absorption of NGF into the blood stream, from the nasal compartment, has been shown. The fact that the NGF mutation R100W appears to separate the effects of NGF on CNS development from those involved in the activation of peripheral pain pathways, provides a basis for designing “painless” NGF variant molecules. In Benzoylaconine particular, we demonstrated that the hNGFR100E mutant displays a full neurotrophic activity in cultured neurons, while showing a reduced nociceptive activity in vivo, via a selective alteration of TrkA versus p75NTR binding and signaling. For this reason, we used the R100E hNGF mutants for in vivo studies, demonstrating that hNGFR100E has a nociceptive activity which is much weaker than that of wild type hNGF. For the present study, the R100E mutation was inserted in the context of a recombinant form of human NGF “tagged” with a single residue epitope, which replaces the Pro residue at position 61 of hNGF with Ser residue present in mouse NGF. hNGFP61S “tagged” molecules are equally Ginsenoside-Ro bioactive as hNGF and are selectively detectable against wild type hNGF, with a specific monoclonal antibody.