Study On The Anxiolytic-like Effects Of Compound DAP

The present study investigated the anxiolytic-like effects of compound DAP by means of behavioral pharmacology for the first time. The other central-acting properties of DAP were also examined to see whether clear differences could be observed between it and diazepam.After acute administration, DAP (60 mg/kg) significantly increased the percentage of open arm entries and time in the elevated plus-maze test. DAP (120 mg/kg) prolonged the time spent in light area without altering the locomotor activity of the animals in the light/dark transition test. DAP (60 240 480mg/kg) significantly inhibited stress-induced hyperthermia. DAP (120mg/kg) significantly increased the food intake in a 5-minute period. In the mouse defense test battery: DAP(60 120 240mg/kg) decreased avoidance distance in the predator avoidance test; In the chase test, DAP (30 60mg/kg) decreased the total risk assessment (stops, orientations, reversals) responses; In the straight alley test; DAP (120 mg/kg) decreased the immobility time significantly; In the forced contact test, DAP (60 120 mg/kg) significantly inhibited the total frequency of defensive behavior; In the contextual test, DAP (120 mg/kg) decreased the rear number of mice after contacted with the rat significantly. In the isolation-induced aggression test, DAP (240 480mg/kg) reduced the total fighting time between isolation mouse and intruder mouse. DAP (42 mg/kg) in the HF(high light, familiar), LU (low light, unfamiliar) test condition and DAP (21 42 mg/kg) in the HU (high light, unfamiliar) test condition all significantly increased social interaction time in pairs of rats. DAP (42 mg/kg) caused a significant increase in exploratory head-dip counts and duration in the holeboard test, prolonged the time spent in drinking and shortened the latency to begin to drink significantly in open field drinking test, produced a significant inhibition on freezing time in conditioned fear-induced freezing test. In general, the results shown above indicate that DAP, at specific doses, possesses a wide range of anxiolytic properties in different anxiety models.The results of further study suggested that at doses eliciting the anxiolytic effect, DAP produce neither influence on amobarbital sodium-induced sleeping and motor activity, nor damage on learning and memory. Even at much higher doses (540mg/kg), DAP did not impair muscle tone in the traction test and the inclined plane test. These outputs suggest that DAP has no diazepam-like side-effects, such as over-sedation, amnesia, muscle relaxation and barbiturate potentiation.DAP and diazepam were differentiated in the OABA_A receptor antagonist picrotoxin-induced seizure assay, with diazepam dose dependently antagonizing seizures while DAP was inactive. This suggests that the anxiolytic-like effect target of DAP may be different from that of diazepam.In conclusion, these findings indicate that DAP exhibits an anxiolytic-like effect at given dosage and it may be potential anxiolytic agent with different mechanism contrasted with diazepam.