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Respir Physiol Neurobiol. 2013 Apr 1;186(2):221-8. doi: 10.1016/j.resp.2013.02.020. Epub 2013 Feb 27.

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

Author information

1
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, United States. mhodges@mcw.edu

Abstract

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (p<0.05). There were also minimal effects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (p<0.05). The augmented CO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p<0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat.

PMID:
23454023
PMCID:
PMC4014076
DOI:
10.1016/j.resp.2013.02.020
[Indexed for MEDLINE]
Free PMC Article

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