Objectives: Examine startle response magnitude and prepulse inhibition (PPI) in adolescent male and female Long-Evans rats exposed to PPA as neonates.
Methods: Male and female Long-Evans rat pups were injected subcutaneously twice a day, 6 hours apart, on post-natal days (PND) 0, 2, 4, 6, 8 with either PPA (500 mg/kg) or phosphate buffered saline (PBS). On PND 44-46, animals were placed in a startle apparatus for one 20 min session. Sixty trials were presented: 10 pulse-alone trials followed by 50 startle and prepulse trials - 10 each of pulse alone, no pulse, 73 dB, 76 dB, and 82 dB prepulse-pulse. In Experiment 1, animals were placed in the startle apparatus in the absence of any drug. In Experiment 2, animals were given a challenge injection of PPA (500 mg/kg, IP) and then placed in the startle apparatus.
Results: In Experiment 1, animals that received PPA as pups displayed significantly greater startle responses than animals that received PBS. There were no significant differences between treatment groups in habituation to the acoustic startle. Upon PPA challenge as adolescent, effects of neonatal drug treatment disappeared and a significant sex difference was found, with males displaying greater startle responses than females. In Experiment 2, female rats that received PPA as pups displayed significantly greater % PPI than male rats that received PPA as pups, while there was no difference in rats that received PBS as pups.
Conclusions: PPA administration in developing rat pups produces a hypersensitivity to acoustic stimuli in both male and female adolescent rats. Upon PPA challenge, however, male adolescent rats were hypersensitive compared to females, regardless of neonatal treatment. Increased inhibition is observed only in female rats that received PPA as pups and were challenged. Recurrent PPA administration may mimic recurrent infections of PPA producing gut bacteria in sensitive paediatric populations, offering further support for the PPA rodent model of ASDs.