Me. Bardgett et al., KAINIC ACID DECREASES HIPPOCAMPAL NEURONAL NUMBER AND INCREASES DOPAMINE-RECEPTOR BINDING IN THE NUCLEUS-ACCUMBENS - AN ANIMAL-MODEL OF SCHIZOPHRENIA, Behavioural brain research, 70(2), 1995, pp. 153-164
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.