Abstract
Our previous experiments demonstrated that systemic depletion of serotonin (5-hydroxytryptamine, 5-HT), similar to levels reported in patients with emotional disorders, enhanced glutamateric activity in the lateral nucleus of the amygdala (LA) and potentiated fear behaviors. However, the effects of isolated depletion of 5-HT in the LA, and the molecular mechanisms underlying enhanced glutamatergic activity are unknown. In the present study, we tested the hypothesis that depletion of 5-HT in the LA induces increased fear behavior, and concomitantly enhances glutamate receptor (GluR) expression. Bilateral infusions of 5,7-dihydroxytryptamine (4 μg per side) into the LA produced a regional reduction of serotonergic fibers, resulting in decreased 5-HT concentrations. The induction of low 5-HT in the LA elevated fear-potentiated startle, with a parallel increase in GluR1 mRNA and GluR1 protein expression. These findings suggest that low 5-HT concentrations in the LA may facilitate fear behavior through enhanced GluR-mediated mechanisms. Moreover, our data support a relationship between 5-HT and glutamate in psychopathologies.
Highlights
Despite the growing prevalence of emotional disorders in modern society, the underlying pathophysiology is still unknown
Our preliminary experiments show that systemic depletion of 5-HT can enhance expression of glutamate receptor (GluR) in the amygdala.[16]
Our results showed that reducing levels of 5-HT in the amygdala could potentiate amygdala glutamatergic neurotransmission and promote fear behaviors
Summary
Despite the growing prevalence of emotional disorders in modern society, the underlying pathophysiology is still unknown. Experiments in animal models show that kindling-induced hyperecitability in the amygdala can potentiate abnormal emotional behaviors.[4] This evidence supports the possibility that emotional disorders involve neuronal hyperexcitability in the amygdala. Many phenotypes can facilitate neuronal hyperexcitability such as low serotonin (5-hydroxytryptamine; 5-HT), a hallmark characteristic of patients with emotional disorders.[5] Previous studies in rodent models demonstrate that systemic depletion of 5-HT can induce functional changes in the amygdala, including increased excitatory post-synaptic potentials and burst firing.[6,7] animals with lower 5-HT levels exhibit increased aggressive behaviors and enhanced fear-potentiated startle (FPS).[1,8] These studies suggest that low 5-HT facilitates abnormal emotional behavior through an induction of neuronal hyperexcitability in the amygdala
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