Hippocampal serotonin-1A receptor function in a mouse model of anxiety induced by long-term voluntary wheel running

We have recently demonstrated that, in C57/Bl6 mice, long-term voluntary wheel running is anxiogenic, and focal hippocampal irradiation prevents the increase in anxiety-like behaviors and neurobiological changes in the hippocampus induced by wheel running. Evidence supports a role of hippocampal 5-HT_1A receptors in anxiety. Therefore, we investigated hippocampal binding and function of 5-HT_1A receptors in this mouse model of anxiety. Four weeks of voluntary wheel running resulted in hippocampal subregion-specific changes in 5-HT_1A receptor binding sites and function, as measured by autoradiography of [³H] 8-hydroxy-2-(di-n-propylamino)tetralin binding and agonist-stimulated binding of [³⁵S]GTPγS to G proteins, respectively. In the dorsal CA1 region, 5-HT_1A receptor binding and function were not altered by wheel running or irradiation. In the dorsal dentate gyrus and CA2/3 region, 5-HT_1A receptor function was decreased by not only running but also irradiation. In the ventral pyramidal layer, wheel running resulted in a decrease of 5-HT_1A receptor function, which was prevented by irradiation. Neither irradiation nor wheel running affected 5-HT_1A receptors in medial prefrontal cortex or in the dorsal or median raphe nuclei. Our data indicate that downregulation of 5-HT_1A receptor function in ventral pyramidal layer may play a role in anxiety-like behavior induced by wheel running.