Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Citalopram reduces glutamatergic synaptic transmission in the auditory cortex via activation of 5-HT1A receptors

Cervantes-Ramírez, Víctora; Canto-Bustos, Marthaa; Aguilar-Magaña, Dianaa; Pérez-Padilla, Elsy Arleneb; Góngora-Alfaro, José Luisa; Pineda, Juan Carlosa; Atzori, Marcoc; Salgado, Humbertoa

doi: 10.1097/WNR.0000000000001366
Cellular, Molecular and Developmental Neuroscience

Serotonin modulates cognitive processes and is related to various psychiatric disorders, including major depression. Administration of citalopram reduces the amplitude of auditory evoked potentials in depressed people and animal models, suggesting that 5-HT has an inhibitory role. Here, we characterize the modulation of excitatory post-synaptic currents by application of either 5-HT or agonists of 5-HT1A and 5-HT2 receptors, or by endogenous 5-HT evoked by citalopram on pyramidal neurons from layer II/III of rat auditory cortex. We found that application of 5-HT concentration-dependently reduces excitatory post-synaptic currents amplitude without changing the paired-pulse ratio, suggesting a post-synaptic modulation. We observed that selective agonists of 5-HT1A and 5-HT2 receptors [8-OH-DPAT (10 µM) and DOI (10 µM), respectively] mimic the effect of 5-HT on the excitatory post-synaptic currents. Effect of 5-HT was entirely blocked by co-application of the antagonists NAN-190 (1 µM) and ritanserin (200 nM). Similarly, citalopram application (1 μM) reduced the amplitude of the evoked excitatory post-synaptic currents. Reduction in the magnitude of the excitatory post-synaptic currents by endogenous 5-HT was interpolated in the dose-response curve elicited by exogenous 5-HT, yielding that citalopram raised the extracellular 5-HT concentration to 823 nM. Effect of citalopram was blocked by the previous application of NAN-190 but not ritanserin, indicating that citalopram reduces glutamatergic synaptic transmission via 5-HT1A receptors in layer II/III of the auditory cortex. These results suggest that the local activity of 5-HT contributes to decrease in the basal excitability of the auditory cortex for enhancing the detection of external relevant acoustic signals.

aDepartment of Neuroscience, Center for Regional Research ‘Dr. Hideyo Noguchi’, Autonomous University of Yucatán

bFaculty of Medicine, Autonomous University of Yucatán, Mérida, Yucatán

cFaculty of Science, Autonomous University of San Luis Potosí, San Luis Potosí, México

Received 28 August 2019 Accepted 3 October 2019

Correspondence to Humberto Salgado, PhD, Laboratorio de Neuroplasticidad, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Av. Itzáes No. 490 por 59 col. Centro, Mérida, Yucatán, México, C.P. 97000, Tel: +52 9999245809; fax: +52 9999236120; e-mail:

© 2019 Wolters Kluwer Health | Lippincott Williams & Wilkins