Alterations of the dopaminergic and glutamatergic neurotransmission in adult rats with postnatal ibotenic acid hippocampal lesion.
In 6-week and 8-week-old rats (pre- and post-pubertally) with neonatal excitotoxic lesions of the ventral hippocampus with ibotenic acid (IBO), we have studied apomorphine-induced motor activity and glutamate and dopamine D1 and D2 binding sites in the hippocampus, striatum, nc. accumbens and frontal cortex as well as K+ -stimulated (3H)-D-aspartate release from hippocampal and frontal cortical slices. Specific glutamate binding was enhanced in the frontal cortex of 8-week-old IBO-treated animals, whereas that in other brain regions remained unchanged. Both D1 and D2 binding sites were downregulated in the striatum without changes in other brain structures. In 6-week-old rats, neither the glutamate nor the dopamine binding sites were altered. The amino acid release from hippocampal and frontal cortical slices of adult IBO treated rats was significantly decreased in comparison to controls, whereas in 6-week-old rats, no significant alterations were detectable. The additionally monitored motor activity was enhanced only in adult IBO-lesioned rats after apomorphine pretreatment. The present data are in agreement with the hypothesis of hyperactive dopamine and hypoactive glutamate systems in schizophrenia and are discussed in the light of schizophrenia-like behavioral changes in rats after postnatal hippocampal IBO lesion.
Schroeder
H
H
Institute of Pharmacology and Toxicology, Medical Faculty, Magdeburg, Germany. helmut.schroeder@medizin.uni-magdeburg.de
Grecksch
G
G
Becker
A
A
Bogerts
B
B
Hoellt
V
V
D000367:Age Factors; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000737:chemistry*; D018491:Dopamine Agonists / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid / Q000032:analysis*; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects; D007051:Ibotenic Acid; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000032:analysis* / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000187:drug effects; D013570:Synaptic Membranes / Q000737:chemistry*; D009435:Synaptic Transmission
D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007051:Ibotenic Acid; D018698:Glutamic Acid; D001058:Apomorphine