Author(s): Jiang X, Xing G, Yang C, Verma A, Zhang L, , Jiang X, Xing G, Yang C, Verma A, Zhang L,
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Abstract The occurrence of stress and anxiety disorders has been closely associated with alterations of the amygdala GABAergic system. In these disorders, dysregulation of the serotonergic system, a very important modulator of the amygdala GABAergic system, is also well recognized. The present study, utilizing a learned helplessness stress rat model, was designed to determine whether stress is capable of altering serotonergic modulation of the amygdala GABAergic system. In control rats, administration of 5-HT or alpha-methyl-5-HT, a 5-HT(2) receptor agonist, to basolateral amygdala (BLA) slices dramatically enhanced frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). This effect was blocked by selective 5-HT(2A) receptor antagonists while a selective 5-HT(2B) receptor agonist and a selective 5-HT(2C) receptor agonist were without effect on sIPSCs. Double immunofluorescence labeling demonstrated that the 5-HT(2A) receptor is primarily localized to parvalbumin-containing BLA interneurons. Thus, serotonin primarily acts via 5-HT(2A) receptors to facilitate BLA GABAergic inhibition. In stressed rats, the 5-HT(2A) receptor-mediated facilitative actions were severely impaired. Quantitative RT-PCR and western blot analysis showed that the impairment of 5-HT(2A) receptor signaling primarily resulted from receptor downregulation. The stress-induced effect appeared to be specific to 5-HT(2A) receptors because stress had no significant impact on other serotonin receptors, as well as histamine H(3) receptor and alpha(2) adrenoceptor signaling in the BLA. This severe impairment of 5-HT(2A) receptor-mediated facilitation of BLA GABAergic inhibition might result in an amygdala circuitry with hyperexcitability, and a lower threshold of activation, and thus be an important mechanism underlying the emergence of stress-associated psychiatric symptoms.
This article was published in Neuropsychopharmacology
and referenced in Journal of Psychiatry