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

NEUROPHARMACOLOGY

卷:139

Article

Gasull-Camos, Julia^1,2,3,4  Martinez-Torres, Sara^5,6  Tarres-Gatius, Mireia^1,2,4  Ozaita, Andres^5,6,7  Artigas, Francesc^1,2,3  Castane, Anna^1,2,3 

[1] CSIC Inst Invest Biomed Barcelona, Dept Neuroquim & Neurofarmacol, Barcelona, Spain

[2] Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain

[3] Inst Salud Carlos III, Ctr Invest Biomed Red Salud Mental, Madrid, Spain

[4] Univ Barcelona, Barcelona, Spain

[5] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain

[6] Inst Salud Carlos III, Red Trastornos Adict, Madrid, Spain

[7] Inst Hosp Mar Invest Med, Barcelona, Spain

关键词: Antidepressant effects;    Dihydrokainic acid;    Dorsal raphe;    GLT-1;    Infralimbic cortex;    Serotonin;   

DOI  :  10.1016/j.neuropharm.2018.06.029

来源: Elsevier

【 摘 要 】

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. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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