ABSTRACT
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.
Subject(s)
Hippocampus , Receptors, N-Methyl-D-Aspartate/metabolism , Schizophrenia , Animals , Habituation, Psychophysiologic , Hippocampus/metabolism , Hippocampus/pathology , Hippocampus/physiopathology , Male , Neural Inhibition/physiology , Pyramidal Tracts/metabolism , Pyramidal Tracts/pathology , Pyramidal Tracts/physiopathology , Rats , Rats, Sprague-Dawley , Reflex, Startle/physiology , Schizophrenia/diagnosis , Schizophrenia/metabolism , Schizophrenia/physiopathologyABSTRACT
Unilateral temporal lobectomy to treat seizure disorders in humans often results in cognitive impairment after the surgery. To determine the potential utility of a rodent model of unilaterally induced cognitive deficits, the present experiment evaluated spatial cognition in adult rats after either left or right hemisphere lesioning of temporal neocortex and underlying hippocampal regions. Evaluation of performance in the eight arm radial maze revealed that both lesioned groups committed more reference memory errors than did nonoperated controls. Working memory errors did not differ statistically between groups. The production of a spatial learning deficit by unilateral damage suggests that this rodent model could serve to test potential improvements in interventional strategies aimed at attenuating cognitive effects of the surgical treatment.
Subject(s)
Cognition Disorders/physiopathology , Functional Laterality/physiology , Hippocampus/injuries , Hippocampus/physiology , Space Perception/physiology , Animals , Behavior, Animal/physiology , Cerebral Decortication , Disease Models, Animal , Male , Memory/physiology , Rats , Rats, Sprague-Dawley , Synapses/physiology , Temporal Lobe/physiologyABSTRACT
Stress has long been recognized as a factor that contributes to the induction of schizophrenia and results in abnormal sensorimotor functioning and information processing. Patients with schizophrenia show disrupted habituation and prepulse inhibition of the acoustic startle response. This study examined the effects of maternal isolation in rats on the habituation of startle and PPI to assess the potential impact of developmental stress on schizophrenic symptomatology. Evaluation of performance in young adulthood (3-4 months) revealed a disruption of habituation in the isolated group; response amplitude increased over time. PPI was not altered. These results suggest that the disruption of habituation may involve acute effects of elevated stress hormones on neuronal functions. In contrast, disturbance of PPI may require an accrual of neuronal insult and damage to ultimately undermine neurologic function, possibly through impact on N-methyl-D-aspartate-mediated transmission. An analysis of effects at middle age is planned to address this possibility.
