Neonatal exposure to MK801 promotes prepulse-induced delay in startle response time in adult rats
- 30 June 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Experimental Brain Research
- Vol. 197 (3), 215-222
- https://doi.org/10.1007/s00221-009-1906-2
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- NMDAR blockade-induced neonatal brain injury: Reversal by the calcium channel agonist BayK 8644Neuroscience Letters, 2008
- Neonatal PCP Is More Potent than Ketamine at Modifying Preweaning Behaviors of Sprague-Dawley RatsToxicological Sciences, 2008
- Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later RecoveryCellular and Molecular Neurobiology, 2008
- Loss of calcium and increased apoptosis within the same neuronBrain Research, 2006
- Widespread Neonatal Brain Damage following Calcium Channel BlockadeDevelopmental Neuroscience, 2006
- Neonatal exposure to MK801 induces structural reorganization of the central nervous systemNeuroReport, 2006
- Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administrationBehavioural Brain Research, 2004
- Development of auditory brainstem circuitryCell and tissue research, 1999
- Short Lead Interval Startle ModificationPublished by Cambridge University Press (CUP) ,1999
- On the Plausibility of “The Neurodevelopmental Hypothesis” of SchizophreniaNeuropsychopharmacology, 1996