Contributions of hippocampal cellular damage and NMDA receptor dysfunction to behavioral markers of schizophrenia.
Pathological changes in the hippocampal formation have been noted in schizophrenic patients and manipulation of neurochemical functions within the limbic system has been shown to yield behavioral changes consistent with schizophrenia. The present study evaluated the impact of kainic acid induced hippocampal cellular damage and manipulation of NMDA receptor function (agonism and antagonism) on common behavioral markers of schizophrenia (habituation and prepulse inhibition of the acoustic startle response in rats). Cellular damage significantly impaired habituation and NMDA antagonism disrupted prepulse inhibition. Damage induced impairment of habituation is consistent with effects on latent inhibition (which is also unaffected by NMDA antagonism) while the antagonist disruption of prepulse inhibition is consistent with effects on associative plasticity. The current findings provide further support for a diverse neurobiological substrate of schizophrenic symptoms suggesting that pharmacologic intervention may need to be multifaceted and could involve competing mechanisms. Cognitive impairments may reflect diminished NMDA receptor function whereas positive symptoms may reflect heightened engagement of anatomically disturbed cellular elements.
Finamore
T L
TL
Department of Psychology, Kent State University, Kent, OH 44242, USA. tfinamor@kent.edu
Seybold
K S
KS
Noble
M
M
Port
R L
RL
D000818:Animals; D006185:Habituation, Psychophysiologic; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology
D016194:Receptors, N-Methyl-D-Aspartate