Acute Fluoxetine (FLX) Administration Improves Inspiratory Motor Activity Response to Acute Single Bout Combined Hypoxic‐Hypercapnic Exposure in Urethane‐anesthetized Spontaneously Breathing Adult Male Sprague‐Dawley Rat at 24‐hr Post‐Lipopolysaccharide (LPS) Injection
Authors: Rodriguez James I , Solomon Irene C 
Published: June 2021

LPS‐induced neuroinflammation has been suggested to alter serotonergic (5‐HT) neurotransmission by acting on the serotonin transporter to alter serotonin levels. In the respiratory neural control system, LPS‐induced neuroinflammation has been shown to affect multiple aspects of central ventilatory control, including 5‐HT‐dependent inspiratory motor behaviors. Ongoing work in our laboratory has been examining the impact of LPS‐induced neuroinflammation on neural control of breathing, including 5‐HT‐mediated inspiratory motor behaviors. Here, we examine the effects of acute systemic administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine hydrochloride (FLX) on basal inspiratory (diaphragm) EMG activity and the maximal chemoreceptor stimulation ventilatory response (MCVR) elicited by an acute single bout of combined hypoxic‐hypercapnic exposure in spontaneously breathing urethane‐anesthetized adult male Sprague‐Dawley rats 24‐hr after systemic LPS (3 mg/kg, ip) or vehicle (0.9% saline, ip) administration. For these experiments, basal diaphragm EMG activity was recorded for 30 min under baseline (BL) conditions (40% O2), FLX (10 mg/kg, iv) was then administered and allowed to exert its effects for 30 min, after which a 3 min MCVR (12% O2, 7%CO2) challenge was performed, followed by 30 min recovery; control experiments using vehicle (VEH; 0.9% saline) instead of FLX were also performed. We found that FLX and VEH administration were ineffective in producing significant changes in inspiratory burst amplitude or frequency in either 24‐hr post‐LPS‐ or saline‐treated rats although during the first 30–60s following FLX injection, a small transient increase (~10–15%) in burst frequency was noted for both groups. In 24‐hr post‐LPS‐ and saline‐treated rats, for the MCVR following VEH injection, most rats exhibited a sustained increase in burst amplitude (≥30% above BL) and a robust increase in burst frequency (~15–30%) that gradually returned to BL levels before the end of the challenge. In 24‐hr post‐LPS and saline‐treated rats, for the MCVR following FLX injection, a robust and maintained increase in burst amplitude (40–50% above FLX level) was also observed; however, marked differences were noted for the MCVR frequency behavior. In this case, in 24‐hr post‐saline‐treated rats, the increase in burst frequency degraded as the challenge progressed (40% above FLX level during min 1 but 97% of FLX level during min 3) while in 24‐hr post‐LPS‐treated rats, the increase in burst frequency remained relatively stable (~25% above FLX level during min 1 and ~20% above FLX level during min 3). These preliminary observations suggest that (compared to control rats), acute FLX administration following systemic LPS‐induced neuroinflammation may be capable of improving inspiratory motor deficits in hypoxic‐hypercapnic chemical control of breathing.

Support or Funding Information

NIH NS101737; Thomas Hartman Center for Parkinson's Disease Research at Stony Brook University

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.