Effects of chronic lithium treatment on ornithine decarboxylase induction and excitotoxic neuropathology in the rat.
Young adult rats were chronically treated with lithium (2.5 mmol/kg/day) for 16 days. The day after the last lithium administration, rats were injected s.c. with the excitotoxic convulsant kainic acid (10 mg/kg). As compared to saline controls, lithium-treated rats had no apparent attenuation of convulsions. Furthermore, the induction of brain ornithine decarboxylase and the consequent increase of putrescine levels, an index related to the convulsant effects of kainic acid, were similar in saline- and lithium-treated rats. Other rats were unilaterally injected with ibotenic acid into the nucleus basalis magnocellularis: no differences were measured in cortical choline acetyltransferase (ChAT) decrease among saline- and lithium-treated rats. In both the above experiments, apoptotic cell death was monitored in relevant brain regions of saline- or lithium-treated rats through a specific in situ labeling method for fragmented DNA. Whilst morphological evidence for a reduced damage in the olfactory cortex and hippocampus of kainic acid-injected rats was not obtained, lithium-treated rats showed a lower decrease of specific neurochemical markers: [3H]D-aspartate uptake and glutamate decarboxylase. This result suggests that mechanisms of recovery, absent in saline-treated animals, are elicited by the excitotoxic insult in lithium-treated rats.
Sparapani
M
M
Department of Biology, University of Bologna, Italy.
Virgili
M
M
Ortali
F
F
Contestabile
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity; D018846:Excitatory Amino Acids / Q000008:administration & dosage / Q000633:toxicity*; D006651:Histocytochemistry; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000633:toxicity; D007267:Injections; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity; D008094:Lithium / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010275:Parasympathetic Nervous System; D016548:Prosencephalon; D051381:Rats; D017208:Rats, Wistar
D018690:Excitatory Amino Acid Agonists; D018846:Excitatory Amino Acids; D007051:Ibotenic Acid; D008094:Lithium; D009955:Ornithine Decarboxylase; D007608:Kainic Acid