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5-HT receptor subtypes involved in the anxiogenic-like action and associated Fos response of acute fluoxetine treatment in rats

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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-HT2C/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.

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Acknowledgement

This study was supported by a grant of the Österreichische Nationalbank ÖNB (N.S.).

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  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

    Peter Salchner & Nicolas Singewald

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  1. Peter Salchner
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  2. Nicolas Singewald
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Correspondence to Nicolas Singewald.

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Salchner, P., Singewald, N. 5-HT receptor subtypes involved in the anxiogenic-like action and associated Fos response of acute fluoxetine treatment in rats. Psychopharmacology 185, 282–288 (2006). https://doi.org/10.1007/s00213-005-0247-5

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  • DOI: https://doi.org/10.1007/s00213-005-0247-5

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