title: Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.
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.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, United States. mhodges@mcw.edu
authors: Matthew R
authors: MR
authors: Hodges
authors: Ashley E
authors: AE
authors: Echert
authors: Madeleine M
authors: MM
authors: Puissant
authors: Gary C
authors: GC
authors: Mouradian
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D012123:Pulmonary Ventilation / Q000187:drug effects*; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D002245:Carbon Dioxide; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors