Details

Autor(en) / Beteiligte

• Gasull-Camós, Júlia
• Martínez-Torres, Sara
• Tarrés-Gatius, Mireia
• Ozaita, Andrés
• Artigas, Francesc
• Castañé, Anna

Titel

Serotonergic mechanisms involved in antidepressant-like responses evoked by GLT-1 blockade in rat infralimbic cortex

Ist Teil von

• Neuropharmacology, 2018-09, Vol.139, p.41-51

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Novel fast-acting antidepressant strategies, such as ketamine and deep brain stimulation, enhance glutamatergic neurotransmission in medial prefrontal cortex (mPFC) regions via AMPA receptor (AMPA-R) activation. We recently reported that the regionally-selective blockade of the glial glutamate transporter-1 (GLT-1) by dihydrokainic acid (DHK) microinfusion in rat infralimbic cortex (IL), the most ventral part of the mPFC, evoked immediate (10 min) antidepressant-like responses, which involved AMPA-R activation and were associated to increased serotonin (5-hydroxytryptamine, 5-HT) release. Given the reciprocal connectivity between the mPFC and the serotonergic dorsal raphe nucleus (DR), here we examined the serotoninergic mechanisms involved in the reported antidepressant-like responses of DHK microinfusion. First, we show that antidepressant-like responses evoked by IL application of DHK and citalopram are mediated by local 5-HT1A receptors (5-HT1A-R), since they are cancelled by previous IL WAY100635 microinfusion. Second, IL DHK microinfusion increases excitatory inputs onto DR, as shown by an increased glutamate and 5-HT release in DR and by a selective increase of c-Fos expression in DR 5-HT neurons, not occurring in putative GABAergic neurons. This view is also supported by an increased 5-HT release in ventral hippocampus following IL DHK microinfusion. Interestingly, antidepressant-like responses evoked by IL DHK lasted for 2 h and could be prolonged for up to 24 h by attenuating self-inhibitory effects via 5-HT1A autoreceptors. In contrast, the antidepressant-like effects of S-AMPA microinfusion in IL were short-lasting. Together, our results further support a prominent role of the IL–DR pathway and of ascending 5-HT pathways in mediating antidepressant-like responses evoked by glutamatergic mechanisms. •IL 5-HT1A-R mediate the antidepressant responses evoked by enhanced IL glutamate.•Enhancing glutamate transmission in IL activates excitatory inputs onto 5-HT neurons.•This effect enhances forebrain 5-HT release via IL-DR reciprocal connectivity.•GLT-1 blockade in IL induces parallel changes in behavior and 5-HT neurochemistry.