ANTIDEPRESSANT-LIKE EFFECTS OF BUSPIRONE MEDIATED BY THE 5-HT1A POSTSYNAPTIC RECEPTORS IN THE LEARNED HELPLESSNESS PARADIGM

The 5-HT1A receptor agonists buspirone and 8-OH-DPAT have strong effects on serotoninergic systems. Mediated by both pre- and post-synaptic 5-HT1A receptors, these pharmacological effects might predict both antidepressant and antianxiety activities. In animal models sensitive to antidepressant drugs, the 5-HT1A agonists administered i.p. have been shown to mimic the behavioral effects of tricyclics. In the present study, the learned helplessness paradigm was used to assess the possible role of pre- or post-synaptic 5-HT1A receptors in this effect. The ability of buspirone compared with 8-OH-DPAT to reduce helpless behavior was investigated after local microinjections (0.1 or 1.0-mu-g in 0.5-mu-l) into the raphe nuclei or into the septum. The results indicate that microinjections of buspirone or 8-OH-DPAT into the raphe nuclei did not reverse helpless behavior; in contrast, microinjections of both 5-HT1A agonists into the septum reverse helpless behavior. These results suggest that antidepressant-like properties of buspirone and 8-OH-DPAT may be mediated, in this test, by the post-synaptic 5-HT1A receptors through functional enhancement of the 5-HT transmission.