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Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats. Respir Physiol Neurobiol 2013 Apr 01;186(2):221-8

Date

03/05/2013

Pubmed ID

23454023

Pubmed Central ID

PMC4014076

DOI

10.1016/j.resp.2013.02.020

Scopus ID

2-s2.0-84875340882 (requires institutional sign-in at Scopus site)   18 Citations

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.

Author List

Hodges MR, Echert AE, Puissant MM, Mouradian GC Jr

Authors

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
Gary C. Mouradian PhD Assistant Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carbon Dioxide
Fluoxetine
Hypercapnia
Male
Pulmonary Ventilation
Rats
Rats, Inbred BN
Rats, Sprague-Dawley
Respiratory Mechanics
Serotonin