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/da y) for 16 days. The day after the last lithium administration, rats we re injected s.c. with the excitotoxic convulsant kainic acid (10 mg/kg ). As compared to saline controls, lithium-treated rats had no apparen t attenuation of convulsions. Furthermore, the induction of brain orni thine decarboxylase and the consequent increase of putrescine levels, an index related to the convulsant effects of kainic acid, were simila r in saline-and lithium-treated rats. Other rats were unilaterally inj ected 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 exp eriments, 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 reduce d damage in the olfactory cortex and hippocampus of kainic acid-inject ed rats was not obtained, lithium-treated rats showed a lower decrease of specific neurochemical markers: [H-3]D-aspartate uptake and glutam ate decarboxylase. This result suggests that mechanisms of recovery, a bsent in saline-treated animals, are elicited by the excitotoxic insul t in lithium-treated rats. (C) 1997 Elsevier Science B.V.