KAINIC ACID DECREASES HIPPOCAMPAL NEURONAL NUMBER AND INCREASES DOPAMINE-RECEPTOR BINDING IN THE NUCLEUS-ACCUMBENS - AN ANIMAL-MODEL OF SCHIZOPHRENIA

Intracerebroventricular (i.c.v.) administration of kainic acid (KA) pr oduces graded neuronal loss in the hippocampus and other regions of th e medial temporal lobe. Many of these brain regions send excitatory pr ojections to the nucleus accumbens, a dopaminergic brain area implicat ed in psychotomimetic and antipsychotic drug action. In the present st udy, neurochemical function in the nucleus accumbens and anterior caud ate-putamen was examined one week after i.c.v. administration of 1.5, 4.5, or 6.6 nmol of KA. As expected, i.c.v. KA produced dose-dependent neuronal loss in the dorsal and ventral hippocampus. Extrahippocampal neuronal loss was also observed in the thalamus and piriform cortex i n some of the KA-treated rats. While ambient levels of dopamine turnov er and excitatory amino acids in the nucleus accumbens were unaltered by KA, administration of the highest KA dose elevated [H-3]spiperone b inding exclusively in the accumbens. Finally, behavioral hyperactivity was observed in KA-treated rats over a five-week period following i.c .v. administration. The pattern of neuronal loss, receptor upregulatio n, and behavioral hyperactivity found after i.c.v. KA administration m ay provide a useful animal model of the limbic neuropathology and neur ochemical dysfunction associated with schizophrenia.