PMID- 21779782 OWN - NLM STAT- MEDLINE DCOM- 20120924 LR - 20211020 IS - 1432-2072 (Electronic) IS - 0033-3158 (Print) IS - 0033-3158 (Linking) VI - 219 IP - 3 DP - 2012 Feb TI - Antidepressant-like properties of oral riluzole and utility of incentive disengagement models of depression in mice. PG - 805-14 LID - 10.1007/s00213-011-2403-4 [doi] AB - RATIONALE: The neuroprotective agent riluzole has antidepressant-like properties in humans, but its mechanisms of action are unclear. Despite the increasing utility of transgenic and knockout mice in addressing such issues, previous studies aimed at characterizing biochemical mechanisms have been conducted in rats. OBJECTIVES: We sought to optimize an oral riluzole administration protocol with antidepressant-like consequences in C57BL/6 mice, a common background strain in genetically modified mice. METHODS: Riluzole (6-60 mug/ml) was dissolved in tap water and replaced regular drinking water for up to 3 weeks; sensitivity to tail suspension, forced swimming, and the locomotor response to extinction training in a model of "incentive disengagement" were tested. Peripheral and central effects of long-term 60-mug/ml treatment were also evaluated. RESULTS: Riluzole had dose-dependent antidepressant-like effects in the forced swim test, and like chronic fluoxetine, exerted antidepressant-like actions in an adaptation of the "incentive disengagement" model at the highest concentration tested. This 60-mug/ml concentration also restored hippocampal brain-derived neuroptrophic factor (BDNF) expression after chronic corticosteroid exposure and increased glutamate glial transporter 1 (GLT-1, or EAAT2) expression without significantly affecting baseline locomotor activity, thymus and adrenal gland weights, or blood serum corticosterone. The lowest 6-mug/ml concentration increased locomotor activity, potentially consistent with an anxiolytic-like effect. CONCLUSIONS: Riluzole's therapeutic potential for treating mood disorders may involve GLT-1 and BDNF, and we suggest this protocol could be used to further characterize its precise long-term biochemical mechanisms of action in animal models of depression. FAU - Gourley, Shannon L AU - Gourley SL AD - Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, CT 06511, USA. shannon.l.gourley@emory.edu FAU - Espitia, Jonathan W AU - Espitia JW FAU - Sanacora, Gerard AU - Sanacora G FAU - Taylor, Jane R AU - Taylor JR LA - eng GR - R01 DA015222/DA/NIDA NIH HHS/United States GR - AA017537/AA/NIAAA NIH HHS/United States GR - MH081211/MH/NIMH NIH HHS/United States GR - UL1 DE019586/DE/NIDCR NIH HHS/United States GR - RL1 AA017537/AA/NIAAA NIH HHS/United States GR - R01 DA011717/DA/NIDA NIH HHS/United States GR - R01 MH081211/MH/NIMH NIH HHS/United States GR - F31 MH079680/MH/NIMH NIH HHS/United States GR - UL1-DE19586/DE/NIDCR NIH HHS/United States GR - MH079680/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110721 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Slc1a2 protein, mouse) RN - 7LJ087RS6F (Riluzole) SB - IM MH - Administration, Oral MH - Animals MH - Antidepressive Agents/*administration & dosage MH - Brain-Derived Neurotrophic Factor/metabolism MH - Depression/*drug therapy/genetics/psychology MH - *Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Excitatory Amino Acid Transporter 2/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Motivation MH - Riluzole/*administration & dosage PMC - PMC3674097 MID - NIHMS470087 EDAT- 2011/07/23 06:00 MHDA- 2012/09/25 06:00 PMCR- 2013/06/05 CRDT- 2011/07/23 06:00 PHST- 2010/01/28 00:00 [received] PHST- 2011/06/30 00:00 [accepted] PHST- 2011/07/23 06:00 [entrez] PHST- 2011/07/23 06:00 [pubmed] PHST- 2012/09/25 06:00 [medline] PHST- 2013/06/05 00:00 [pmc-release] AID - 10.1007/s00213-011-2403-4 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2012 Feb;219(3):805-14. doi: 10.1007/s00213-011-2403-4. Epub 2011 Jul 21.