Acute or chronic lithium does not affect agonist-stimulated inositol trisphosphate formation in rat brain in vivo

Rats were given lithium either acutely by s.c. injection (4 m eq kg^-1) or chronically by including 0.2% LiCl in their diet for 3 weeks. Microdialysis probes were inserted into the cortex or hippocampus, using re-usable guides, and perfused with artificial CSF. Fractions were collected beginning 18 h after the end of treatment and were analysed for inositol trisphosphate (IP₃). Neither acute nor chronic treatment affected basal levels of IP₃ or stimulation of IP₃ formation by either carbachol or noradrenaline in the hippocampus. Similarly, neither basal nor carbachol-stimulated IP₃ levels in rat cortex were affected by acute Li administration. It would appear that the reductions in these parameters previously reported by other workers using brain slices were due to inositol depletion occurring at the stage of brain slice preparation. The inositol depletion hypothesis for the mechanism of action of lithium does not therefore appear to be supported by in vivo evidence.