Pre- or postsynaptic activity of 5-HT 1A compounds in mice depends on the anxiety paradigm

Abstract

The purpose of the present study was to compare the contribution of pre and postsynaptic 5-HT 1A receptors to the anxiolytic effects of serotonergic 1A compounds in two animal models of anxiety. To this aim, the 5-HT 1A ligands buspirone, ipsapirone, indorenate, and 8-OH-DPAT were tested in the burying behavior test and the avoidance exploratory behavior 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-HT 1A agonists produced a significant reduction in this behavior in both p-CPA- and 5,7-DHT-lesioned animals. In the exploratory behavior 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-HT 1A compounds in the avoidance exploratory behavior test. Data suggest that the effect of 5-HT 1A compounds in the burying behavior test is mediated via the stimulation of postsynaptic receptors, while in the avoidance exploratory behavior paradigm these compounds act through the stimulation of the presynaptic site. Discussion is based on the differences between the animal models of anxiety.