Lipopolysaccharide produces dose-dependent reductions of the acoustic startle response without impairing prepulse inhibition in male rats

Abstract

This study examined the dose-dependent effects of Lipopolysaccharide (LPS) on the acoustic startle response and prepulse inhibition (PPI) in male Long-Evans rats. LPS is known to stimulate the innate immune system and result in behavior modifications referred to as "sickness behaviors". The purpose of this study was to assess the ability of LPS to modulate sensorimotor reflexes (Startle-Only trials) and/or sensory processing (PPI trials). Rats were injected intraperitoneally with LPS (50, 100 or 200 microg/kg LPS, n=9/group) or saline vehicle (n=14) on 2 test days 72 h apart. Subjects were placed in a familiar startle box apparatus where startle response magnitudes were recorded following 115 dB Startle-Only trials and PPI trials (with prepulses at +3, +6 and +12 dB above background noise). Analysis of Startle-Only trials indicated a significant dose-dependent effect of LPS on Test Day 1. The 200 microg/kg LPS group exhibited significantly reduced startle response magnitude relative to all other treatments. On the PPI trials no LPS groups displayed significantly different performance from vehicle controls. Also, DayxDrug interactions for both Startle-Only and PPI trial types indicated behavioral tolerance to LPS. LPS reduced the acoustic startle response in a dose-dependent manner on Test Day 1. From the PPI data, it is evident that all treatment groups elicited near-normal inhibition levels indicating adequate sensory function. In combination, the results suggest that the range of sickness behaviors following LPS-administration to adult rats includes decreased non-voluntary motor activity as reflected by reduced startle magnitude.