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 CO 2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO 2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO 2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10 mg/(kg day)) 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 ( V T ) was reduced in BN rats ( p 2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and V T during hypercapnia in BN rats ( p 2 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 2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO 2 sensitivity in the BN rat.