Chronic Administration of Fluoxetine Markedly Attenuates the Hypercapnic Ventilatory Response in Urethane‐anesthetized Female Mice

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to treat anxiety disorders in humans, and these agents have been reported to reduce hyperventilation as well as hypersensitivity to increased levels of CO2. In rodent models, conflicting observations regarding the effects of SSRIs have been reported. For example, in unanesthetized male rats, administration of the SSRI fluoxetine hydrochloride (FHCL) is ineffective in altering normocpanic and hypercapnic ventilatory activity while in urethane‐anesthetized male mice, FHCL increases basal breathing frequency. In humans, FHCL has also been shown to differentially affect behavioral and neural function in males vs females. Thus, the current study was undertaken to evaluate the effects of FHCL on ventilatory activity in female mice. To accomplish this, diaphragm EMG activity was recorded in spontaneously breathing urethane‐anesthetized female C57BL/6 mice following 28‐d continuous infusion of FHCL (~2 mg/kg/day, n=5) or vehicle (50% DMSO:50% saline, n=5) under baseline conditions and in response to 7% CO2. We found that 7% CO2 elicited an increase in EMG burst frequency (P<0.05, as expected) in vehicle‐treated mice; however, this increase in burst frequency was markedly attenuated or abolished (P<0.05) in FHCL‐treated mice. These findings suggest that SSRIs may alter the sensitivity to hypercapnia in female mice. Supportedby NS045321