Abstract
Intracerebroventricular (i.c.v.) administration of kainic acid (KA) produces graded neuronal loss in the hippocampus and other regions of the medial temporal lobe. Many of these brain regions send excitatory projections to the nucleus accumbens, a dopaminergic brain area implicated in psychotomimetic and antipsychotic drug action. In the present study, neurochemical function in the nucleus accumbens and anterior caudate-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 in some of the KA-treated rats. While ambient levels of dopamine turnover and excitatory amino acids in the nucleus accumbens were unaltered by KA, administration of the highest KA dose elevated [3H]spiperone binding 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 upregulation, and behavioral hyperactivity found after i.c.v. KA administration may provide a useful animal model of the limbic neuropathology and neurochemical dysfunction associated with schizophrenia.
Original language | English (US) |
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Pages (from-to) | 153-164 |
Number of pages | 12 |
Journal | Behavioural Brain Research |
Volume | 70 |
Issue number | 2 |
DOIs | |
State | Published - Oct 1995 |
Funding
Supportedb y grantsf rom theS cottishR ite Benevolent Foundation’s Schizophrenia Research Program, the Theodore and Vada Stanley Foundation, the NIMH (Research Training Grant (MH14677) and Scientist Development Award (MHOllOg)), and the NIAAA (ResearchT raining Grant AA07144).W e thank Carol Guilliard, John Harding, and April Ratanasadudfio r their technicala ssistancea nd Dr. Tom Corso for his assistancwe ith the photographyW. e also appreciateth e valuablec ommentso f Dr. John W. Olney.
Keywords
- Caudate-putamen
- Dopamine
- Glutamate
- Hippocampus
- Locomotor activity
- Nucleus accumbens
- Rats
- Spiperone
ASJC Scopus subject areas
- Behavioral Neuroscience