Neonatal exposure to MK801 promotes prepulse-induced delay in startle response time in adult rats

Exp Brain Res. 2009 Aug;197(3):215-22. doi: 10.1007/s00221-009-1906-2. Epub 2009 Jun 30.


The acoustic startle reflex in rats can be inhibited if a prepulse stimulus is presented just before the startle stimulus (prepulse inhibition; PPI). When postnatal day 7 (P7) rats are exposed to agents that block the NMDA receptor (NMDAR), robust apoptosis is observed within hours and is thought to be followed at later ages by a significant loss of PPI. To understand these observations further, we exposed rat pups to vehicle or the NMDAR antagonist MK801 (1 mg/kg) at P6, P8, and P10. We then examined animals for PPI at P28 and P56. Compared to vehicle controls, we found no evidence for PPI deficits in the MK801-treated group, although we did observe prepulse-induced delay in response time at P56 (but not at P28). In a parallel study, we also performed histological analysis of brain sections for evidence of the pro-apoptotic marker activated caspase-3, 8 h after vehicle or MK801 injection into P6 animals. We found that there was a robust increase in this marker of cell death in the inferior colliculus of MK801 compared to vehicle-treated animals. Thus, transient blockade of the NMDAR during the postnatal period not only promotes early apoptosis in a brain region critical for acoustic processing but also leads to auditory deficits at a later age, suggesting that injury-induced loss of collicular neurons leads to network reorganization in the auditory system that is progressive in nature.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / physiology
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Auditory Pathways / drug effects*
  • Auditory Pathways / pathology
  • Auditory Pathways / physiopathology
  • Biomarkers / metabolism
  • Caspase 3 / metabolism
  • Dizocilpine Maleate / toxicity*
  • Excitatory Amino Acid Antagonists / toxicity
  • Female
  • Glutamic Acid / metabolism
  • Inferior Colliculi / drug effects*
  • Inferior Colliculi / pathology
  • Inferior Colliculi / physiopathology
  • Male
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Nerve Net / drug effects*
  • Nerve Net / pathology
  • Nerve Net / physiopathology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Sensory Gating / drug effects*
  • Sensory Gating / physiology
  • Time


  • Biomarkers
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Dizocilpine Maleate
  • Caspase 3