TIME-DEPENDENT CHANGES IN GAMMA OSCILLATIONS AND PARVALBUMIN IMMUNOREACTIVE CELL DENSITY IN THE CA2/3 REGION OF THE RAT HIPPOCAMPUS FOLLOWING SUB-CHRONIC PHENCYCLIDINE TREATMENT

RO4583298. Discussion: In the current study, we observed a good correlation between in vivo activity of RO4583298 in gerbil and mouse and its mode of antagonism. The pseudo-irreversible mode of antagonism at gNK1, likely contributed to RO4583298's robust and prolonged in vivo activity in the gerbil NK1 agonist-induced foot tapping model (ID50=0.4 mg/kg, po), while RO4583298's competitive mode of antagonism at mNK3, was demonstrated as a 14-fold higher dose was required to produce in vivo activity in the mouse senktide-induced tail whip model (ID50=5.6 mg/kg, po). In conclusion, RO4583298 is a high affinity, dual antagonist with an apparent non-competitive mode of antagonism and in vivo activity at both NK1 and NK3. Thus, RO4583298 could prove useful when investigating the role of NK1 and NK3 receptors in pathophysiological processes of psychiatric disorders such as anxiety, depression and schizophrenia.