Lipopolysaccharide reduces tactile startle response magnitude but not prepulse inhibition in rats: a dose-response examination.

As a result of innate immune system stimulation, lipopolysaccharide (LPS) exposure produces a range of behavioral modifications referred to as "sickness behaviors." This study assessed the effects of multiple doses of LPS on air-puff tactile startle reflex (Startle-Only trials) and acoustic prepulse inhibition (PPI) in adult male rats. Rats were injected intraperitoneally with LPS (300, 200, 100, or 50 microg/kg LPS, n=9, 10, 10, and 10 respectively) or saline vehicle (n=10) on 2 test days 72 h apart. Magnitude of the startle response was recorded following 15 psi air-puffs (Startle-Only trials) and auditory PPI of the tactile startle response (with prepulses at +3, +6 and +12 dB above background noise). Startle-Only trial analysis suggested a significant dose-dependent effect of LPS on Test Day 1 with the 300 and the 200 microg/kg LPS groups exhibiting significantly reduced startle responses. On the second test day, the control animals displayed significant habituation to the tactile startle stimulus while the LPS animals did not. On the PPI trials, LPS animals exhibited normal prepulse inhibition. The acoustic PPI of the tactile startle response was significantly greater on Test Day 2 than on the first test day, regardless of treatment. These results suggest that "sickness behaviors" induced by high doses of LPS may include decreased non-voluntary motor activity, as measured by the tactile startle response. They also show that sensory processing, as measured by PPI, is not impaired with sickness.