PROGRESSIVE NEURODEGENERATION AFTER INTRACEREBROVENTRICULAR KAINIC ACID ADMINISTRATION IN RATS - IMPLICATIONS FOR SCHIZOPHRENIA

Background: Intracerebroventricular (ICV) administration of kainic aci d to rats produces limbic-cortical neuronal damage that has been compa red to the neuropathology of schizophrenia. Methods: Groups Of adult r ats Mere administered ICV kainic acid and then assessed for neuronal l oss and the expression of proteins relevant to mechanisms of neuronal damage after one and fourteen days, Neuronal loss was assessed by two- dimensional cell counting and protein expression was assessed by immun ohistochemistry,. Results: ICV kainic acid administration was associat ed with both immediate (day I) and delayed (day 14) neuronal loss iii the dorsal hippocampus. The immediate injury tvas largely limited to t he CA3 hippocampal subfield, It while the delayed injury included the CAI subfield. Multiple mechanisms of cell death appeared to be involve d in the delay ed neuronal loss, as evidenced by changes in the expres sion of glutamate receptor subunits, heat shock protein and jun protei n. Conclusions: ICV kainic acid administration to adult rats produces progressive damage to limbic-cortical neurons, involving both fast and slow mechanisms of cell death, Given the evidence for clinical deteri oration, cognitive deficits and hippocampal neuropathy in some cases o f schizophrenia, this animal model may be relevant for hypotheses rega rding mechanisms of neurodegeneration in that disorder. (C) 1998 Socie ty of Biological Psychiatry.