PRESYNAPTIC OR POSTSYNAPTIC ACTIVITY OF 5-HT1A COMPOUNDS IN MICE DEPENDS ON THE ANXIETY PARADIGM

The purpose of the present study was to compare the contribution of pr e and postsynaptic 5-HT1A receptors to the anxiolytic effects of serot onergic(1A) compounds in two animal models of anxiety. To this aim, th e 5-HT1A ligands buspirone, ipsapirone, indorenate, and 8-OH-DPAT were tested in the burying behavior test and the avoidance exploratory beh avior paradigm in control, pCPA-treated, and 5,7-DHT-lesioned mice. p- CPA and 5,7-DHT treatments did not modify the burying behavior per se, while 5-HT1A agonists produced a significant reduction in this behavi or in both p-CPA- and 5,7-DHT-lesioned animals. In the exploratory beh avior paradigm, p-CPA per se but not 5,7-DHT increased the black/white transitions, interpreted as an antianxiety action. The ICV injection of 5,7-DHT blocked such effect of the 5-HT1A compounds in the avoidanc e exploratory behavior test. Data suggest that the effect of 5-HT1A co mpounds in the burying behavior test is mediated via the stimulation o f postsynaptic receptors, while in the avoidance exploratory behavior paradigm these compounds act through the stimulation of the presynapti c site. Discussion is based on the differences between the animal mode ls of anxiety.