title: Neonatal exposure to MK801 promotes prepulse-induced delay in startle response time in adult rats.
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.
authors: Department of Neurobiology and Anatomy, 4100 Gray Bldg, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston Salem, NC 27157-1010, USA.
authors: Amanda
authors: A
authors: Lyall
authors: John
authors: J
authors: Swanson
authors: Chun
authors: C
authors: Liu
authors: Terry D
authors: TD
authors: Blumenthal
authors: Christopher Paul
authors: CP
authors: Turner
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001306:Auditory Pathways / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007245:Inferior Colliculi / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009415:Nerve Net / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D013995:Time
chemical_list: D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D053148:Caspase 3