Anxiolytic properties of the selective, non-peptidergic CRF1 antagonists, CP154,526 and DMP695: A comparison to other classes of anxiolytic agent

The selective, non-peptidergic corticotropin-releasing factor (CRF), recept or antagonists, CP154,526 and DMP695, dose-dependently increased punished r esponses Of rats in a Vogel conflict test and enhanced social interaction ( SI) of rats in an unfamiliar environment. They were, however, inactive in a plus-maze procedure and failed to reduce ultrasonic vocalizations (USV) as sociated with an aversive environment. In contrast, the benzodiazopine, chl ordiazepoxide, was effective in all these procedures. Further, the serotoni n (5-HT)(1A) agonist, flesinoxan, was active in each paradigm (except the p lus-maze) while the 5-HT2C antagonist, SB242,084, was effective in the S1 a nd Vogel but not the plus-maze and USV procedures. In contrast to chlordiaz epoxide, flesinoxan and SB242,084, CP154,526 did not modify dialysate level s of 5-HT, norepinephrine (NE) and dopamine (DA) in the frontal cortex (FCX ) of freely moving rats. In conclusion, CP154,526 and DMP695 possess a comm on and distinctive profile of anxiolytic action expressed in the absence of an intrinsic influence upon monoamine release.