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), receptor antagonists, CP154,526 and DMP695, dose-dependently increased punished responses 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) associated with an aversive environment. In contrast, the benzodiazopine, chlordiazepoxide, was effective in all these procedures. Further, the serotonin (5-HT)(1A) agonist, flesinoxan, was active in each paradigm (except the plus-maze) while the 5-HT2C antagonist, SB242,084, was effective in the S1 and Vogel but not the plus-maze and USV procedures. In contrast to chlordiazepoxide, flesinoxan and SB242,084, CP154,526 did not modify dialysate levels 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 common and distinctive profile of anxiolytic action expressed in the absence of an intrinsic influence upon monoamine release.