The septum and the hippocampus differentially mediate anxiolytic effects of R(+)-8-OH-DPAT.

Infusing the 5-HT1A receptor agonist R(+)-8-OH-DPAT into the septum or hippocampus reduced the fear responses of rats differentially in the elevated plus-maze and shock-probe burying tests, two rat models of anxiety. Intra-septal infusions of R(+)-8-OH-DPAT (5 and 10 microg) produced dramatic reductions in rat burying behavior in the shock-probe test, whereas it did not alter rat open-arm activity in the plus-maze test, across a wide range of doses (0.1, 0.25, 5 and 10 microg). Conversely, intra-hippocampal infusions of R(+)-8-OH-DPAT (0.1 and 5 microg/side) produced substantial increases in open-arm activity in the plus-maze test, but did not alter rat burying behavior in the shock-probe test. These dissociations suggest that 5-HT1A receptors in the septum and hippocampus exert parallel but distinct control over different fear reactions.