5-HT1A receptor agonist affects fear conditioning through stimulations of the postsynaptic 5-HT1A receptors in the hippocampus and amygdala

Abstract

Evidence from preclinical and clinical studies has shown that 5-HT 1A receptor agonists have anxiolytic actions. The anxiolytic actions of 5-HT 1A receptor agonists have been tested by our previous studies using fear conditioning. However, little is known about the brain regions of anxiolytic actions of 5-HT 1A receptor agonists in this paradigm. In the present study, we investigated the effects of bilateral microinjections of flesinoxan, a selective 5-HT 1A receptor agonist, into the hippocampus, amygdala and medial prefrontal cortex on the expression of contextual conditioned freezing and the defecation induced by conditioned fear stress in rats. These results reveal that both intrahippocampal and intraamygdala injections of flesinoxan decreased the expression of conditioned freezing, while injections into the medial prefrontal cortex did not. In addition, intraamygdala injection of flesinoxan attenuated the increased defecation induced by conditioned fear, but injections into the hippocampus and medial prefrontal cortex failed. These results suggest that flesinoxan exerts its anxiolytic actions in the fear conditioning through stimulations of the postsynaptic 5-HT 1A receptors in the hippocampus and amygdala.

Serotonin‐immunoreactive axon terminals innervate pyramidal cells and interneurons in the rat basolateral amygdala

“…DOI 10.1002/cne (Blair et al, 2001), the presynaptic and postsynaptic 5-HT 1A R-mediated inhibitory responses of BLC pyramidal cells revealed by electrophysiological studies are consistent with recent investigations that have demonstrated reductions in long-term potentiation (LTP; Pollandt et al, 2003) and aversive conditioning (Liang et al, 1999, Li et al, 2006 with administration of 5-HT 1A R agonists into the BLC. Fig.…”

Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically

“…In addition, Yamauchi et al (2012) found that systemic administration of mirtazapine increases extracellular 5-HT levels in the dorsal hippocampus but not in the prefrontal cortex. Because the dorsal hippocampus receives projections primarily from the MRN (Vertes et al, 1999), these results support the hypothesis that the serotonergic pathway from the MRN underlies the anxiolytic-like effect of mirtazapine that stimulates the MRN and results in the elevated 5-HT levels in the hippocampus, which lead to the anxiolytic-like effect (Li et al, 2006). However, in the present study, intra-MRN injection of mirtazapine did not significantly reduce contextual conditioned freezing, which is not consistent with our previous finding .…”

Juvenile stress attenuates the dorsal hippocampal postsynaptic 5-HT1A receptor function in adult rats

“…Previous studies have demonstrated the hippocampus and amygdala to play crucial roles in anxiety and fear (LeDoux 2000). Li et al (2006) indicated that the local administration of a 5-HT 1A receptor agonist into the hippocampus and amygdala decreased the freezing behavior in conditioned fear via postsynaptic 5-HT 1A receptors.…”