Peter Salchner1, Nicolas Singewald. 1. Department of Pharmacology and Toxicology, Institute of Pharmacy and Center of Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Peter-Mayr-Strasse 1, 6020 Innsbruck, Austria.
Abstract
RATIONALE: We have recently reported that acute treatment with the selective serotonin reuptake inhibitor fluoxetine exacerbates escape responses to airjet and facilitates airjet-induced activation of locus coeruleus (LC) neurons. OBJECTIVE: Here we aimed to identify the 5-HT receptor subtype(s) mediating the anxiogenic-like effects of acute fluoxetine in this paradigm and to study whether chronic fluoxetine treatment would alter these responses. METHODS: The expression of the immediate early gene c-fos was used as a marker of neuronal activation. RESULTS: Acute fluoxetine increased the airjet-induced escape behaviour and Fos expression in the LC of saline-pretreated rats. Pretreatment with the 5-HT(2C/2B) antagonist SB 206553, but not with the 5-HT1A antagonist WAY 100635, the 5-HT1B antagonist SB 224289 or the 5-HT3 antagonist Y-25130 inhibited the fluoxetine-induced increase in escape behaviour and the associated elevated LC Fos response. The selective 5-HT2C agonist MK-212 mimicked the anxiogenic response of fluoxetine. Chronic treatment with fluoxetine abolished the anxiogenic-like effect and led to a normalization of the enhanced fluoxetine-induced Fos response to airjet. CONCLUSIONS: Taken together, the results indicate that the anxiogenic-like effect as well as the facilitated neuronal reactivity induced by acute fluoxetine in the airjet model is mediated primarily by activation of 5-HT2C receptors.
RATIONALE: We have recently reported that acute treatment with the selective serotonin reuptake inhibitor fluoxetine exacerbates escape responses to airjet and facilitates airjet-induced activation of locus coeruleus (LC) neurons. OBJECTIVE: Here we aimed to identify the 5-HT receptor subtype(s) mediating the anxiogenic-like effects of acute fluoxetine in this paradigm and to study whether chronic fluoxetine treatment would alter these responses. METHODS: The expression of the immediate early gene c-fos was used as a marker of neuronal activation. RESULTS: Acute fluoxetine increased the airjet-induced escape behaviour and Fos expression in the LC of saline-pretreated rats. Pretreatment with the 5-HT(2C/2B) antagonist SB 206553, but not with the 5-HT1A antagonist WAY 100635, the 5-HT1B antagonist SB 224289 or the 5-HT3 antagonist Y-25130 inhibited the fluoxetine-induced increase in escape behaviour and the associated elevated LC Fos response. The selective 5-HT2C agonist MK-212 mimicked the anxiogenic response of fluoxetine. Chronic treatment with fluoxetine abolished the anxiogenic-like effect and led to a normalization of the enhanced fluoxetine-induced Fos response to airjet. CONCLUSIONS: Taken together, the results indicate that the anxiogenic-like effect as well as the facilitated neuronal reactivity induced by acute fluoxetine in the airjet model is mediated primarily by activation of 5-HT2C receptors.
Authors: Belinda J Liddell; Kerri J Brown; Andrew H Kemp; Matthew J Barton; Pritha Das; Anthony Peduto; Evian Gordon; Leanne M Williams Journal: Neuroimage Date: 2005-01-01 Impact factor: 6.556
Authors: Melissa A Birkett; Nina M Shinday; Eileen J Kessler; Jerrold S Meyer; Sarah Ritchie; James K Rowlett Journal: Pharmacol Biochem Behav Date: 2011-03-21 Impact factor: 3.533
Authors: Pablo R Moya; Meredith A Fox; Catherine L Jensen; Justin L Laporte; Helen T French; Jens R Wendland; Dennis L Murphy Journal: BMC Pharmacol Date: 2011-04-07
Authors: Jakob Näslund; Erik Studer; Robert Pettersson; Melker Hagsäter; Staffan Nilsson; Hans Nissbrandt; Elias Eriksson Journal: Int J Neuropsychopharmacol Date: 2015-02-25 Impact factor: 5.176