5-HT receptor subtypes involved in the anxiogenic-like action and associated Fos response of acute fluoxetine treatment in rats.
BACKGROUND
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.
Salchner
Peter
P
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.
Singewald
Nicolas
N
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000145:classification* / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005473:Fluoxetine; D007211:Indoles; D010078:Oxazines; D010879:Piperazines; D010881:Piperidones; D016760:Proto-Oncogene Proteins c-fos; D011719:Pyrazines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013141:Spiro Compounds; C108518:SB 22489G; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C070671:azasetron; C094868:SB 206553