| First Author | García-García AL | Year | 2013 |
| Journal | Neuropharmacology | Volume | 70 |
| Pages | 190-9 | PubMed ID | 23168115 |
| Mgi Jnum | J:318974 | Mgi Id | MGI:6862153 |
| Doi | 10.1016/j.neuropharm.2012.11.005 | Citation | Garcia-Garcia AL, et al. (2013) Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway. Neuropharmacology 70:190-9 |
| abstractText | Unraveling the mechanisms of 5-HT neuron control might provide new insights into depression pathophysiology. In addition to the inhibitory 5-HT1A autoreceptors, cortico-raphe glutamatergic descending pathways are suggested to modulate 5-HT activity in the DRN. Here we studied how decreased VGLUT1 levels in the brain stem affect glutamate regulation of 5-HT function. VGLUT1+/- mice (C57BL/6) and wild type (WT) littermates were used. VGLUT1 expression in the DRN, 5-HT turnover and immuno histochemical analysis of neuronal activity in different areas was studied. Moreover, the functionality of the inhibitory 5-HT1A autoreceptor was assessed using electrophysiological, biochemical and pharmacological approaches. VGLUT1 immunoreactivity was markedly lower in the DRN of the VGLUT1+/- mice and specifically, in the surroundings of GABA and 5-HT cell bodies. These mice showed decreased induced neuronal activity in 5-HT cells bodies and in different forebrain areas, as well as decreased hippocampal cell proliferation and 5-HT turnover. Further, 5-HT1A autoreceptor desensitization was evidenced by electrophysiological studies, GTP-gamma-S coupling to 5-HT1A autoreceptor and a lower hypothermic response to 5-HT1A activation. This study shows first time that VGLUT1 dependent glutamate innervation of the DRN could modulate 5-HT function. |
