Influence of Two‐Hit Lipopolysaccharide (LPS) Administration on 8‐OH DPAT‐induced Inspiratory Burst Amplitude and Frequency Changes in Urethane‐anesthetized Spontaneously Breathing Adult Male Sprague‐Dawley Rat with Prior Single‐Bout Acute Intermittent Hypoxia Exposure
Authors: Thomas Selena C , Bhatt Rashi C , Maqsood Anas , Wadolowski Steven B , Solomon Irene C 
Published: June 2021

Inflammation has been suggested to alter a variety of physiological processes by its effects on serotonergic (5‐HT) neurotransmission. In the respiratory neural control system, LPS‐induced neuroinflammation has been shown to affect multiple aspects of central ventilatory control, including serotonin2 (5‐HT2)‐dependent inspiratory motor behaviors. While numerous studies have focused on the role of 5‐HT2A receptors in neural control of breathing, the roles of other 5‐HT receptors are beginning to be appreciated. To this end, activation of 5‐HT1A receptors has been shown to exert marked effects on inspiratory motor activity; however, the impact of LPS‐induced neuroinflammation on 5‐HT1A receptor‐mediated inspiratory motor behaviors remains to be determined. To begin to address this issue, we studied the effects of systemic application of the 5‐HT1A receptor agonist 8‐hydroxy‐2‐(di‐npropylamino) tetralin (8‐OH DPAT) on basal inspiratory (diaphragm) EMG burst amplitude and frequency in spontaneously breathing urethane‐anesthetized adult male Sprague‐Dawley rats following a ‘two‐hit’ lipopolysaccharide (LPS) administration protocol in which systemic LPS (3 mg/kg, ip) was administered ~24 hr prior to an intratracheal LPS (0.5 mg/kg, IT) injection. Similar 8‐OH DPAT experiments were performed in control rats that were either untreated or received two‐hit saline injections. All rats used for this study had also undergone an acute intermittent hypoxia (AIH) exposure protocol that was completed at least 90 min prior to administration of 8‐OH DPAT. For this study, we compare diaphragm EMG burst activities before (baseline, BL) systemic administration of 8‐OH DPAT (0.3 mg/kg, iv) to those obtained at various time points for the 30 min period immediately following administration. We found that in both control and LPS‐treated rats, administration of 8‐OH DPAT similarly affected burst frequency but differentially affected burst amplitude. In both groups of rats, 8‐OH DPAT injection produced an ~50% increase in burst frequency above BL levels within 30–60s, but by 5 min post injection, this increase was attenuated to an ~30% increase above BL levels that persisted for the remainder of the 30 min recording period. While 8‐OH DPAT injection produced an initial ~15% increase in burst amplitude above BL levels within 60s in both groups of rats, a further increase in burst amplitude up to ~30% above BL was noted by 15 min post injection in control rats, and this increase persisted for the remainder of the 30 min recording period while in LPS‐treated rats, a slight attenuation of the burst amplitude increase was noted. These preliminary observations suggest that (compared to control rats) two‐hit LPS administration may differentially affect mechanisms by which 5‐HT1A receptor activation modulates inspiratory burst frequency and amplitude. Additional experiments will be needed to identify specific mechanisms underlying these differences.Support or Funding InformationNIH NS101737; Thomas Hartman Center for Parkinson's Disease Research at Stony Brook UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.