Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats

• DOI: 10.1038/tp.2017.7
• Publication Date: 2017-02-21T15:39:27Z
• Authors: J Gasull-Camós; M Tarrés-Gatius; F Artigas; A Castañé
• Keywords: NBQX; Infralimbic cortex; Citalopram

Abstract Ketamine and deep brain stimulation produce rapid antidepressant effects in humans rodents. An increased AMPA receptor (AMPA-R) signaling medial prefrontal cortex (mPFC) has been suggested to mediate these responses. However, little research addressed the direct of enhancing glutamate tone or AMPA-R mPFC subdivisions. The current study investigates behavioral neurochemical consequences transporter-1 (GLT-1) blockade s-AMPA microinfusion infralimbic (IL) prelimbic (PrL) cortex. Owing connectivity between raphe nuclei, role serotonin is also explored. bilateral depolarizing agent veratridine into IL -but not PrL- rats evoked immediate antidepressant-like same regional selectivity was observed after dihydrokainic acid (DHK), a selective inhibitor GLT-1, present astrocytes. DHK-evoked responses appear be mediated by an AMPA-R-driven enhancement serotonergic activity, as (i) they were prevented NBQX 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt) mimicked s-AMPA; (ii) DHK elevated similarly extracellular PrL, although 5-HT c-fos expression midbrain dorsal only when agents applied IL; (iii) synthesis inhibition citalopram IL. These results indicate that acute increase glutamatergic neurotransmission selectively triggers rats, likely activation IL–raphe pathways, which then fast activity.