SSRIs are widely used as anxiolytics. Previously, we demonstrated that local injection of an SSRI into the basolateral nucleus of the amygdala (BLA) had anxiolytic effect in rats. In the present study, we investigated the effect of local co-administration of an SSRI and 5-HT_1A or 5-HT_2A antagonists into the BLA on conditioned fear in Wistar/ST rats, and indicated the expression of 5-HT_1A and 5-HT_2A receptor mRNAs in the BLA by in situ hybridization in C57BL/6 mice.
Local injection of citalopram (SSRI) into the BLA attenuated conditioned freezing, and this effect was blocked by local co-administration of WAY100635 (5-HT_1A antagonist) or MDL11939 (5-HT_2A antagonist). In in situ hybridization, 5-HT_1A mRNA was mainly expressed in GABAergic interneurons expressing somatostatin (SOM) mRNA, and 5-HT_2A mRNA was in those expressing parvalbumin (PV) or SOM mRNA.
From these results, it is speculated that SSRIs exert anxiolytic effect via 5-HT_1A and 5-HT_2A receptors in the BLA. Because PV- and SOM-positive GABAergic interneurons are known to form local neural circuits with glutamatergic pyramidal neurons, the anxiolytic action of SSRIs is likely to be mediated by serotonergic modulation of pyramidal neurons via these interneuron subclasses.