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 (4m eq kg(-1) ) or chronically by including 0.2% LiCl in their diet for 3 weeks. Mic rodialysis probes were inserted into the cortex or hippocampus, using re-usable guides, and perfused with artificial CSF. Fractions were col lected beginning 18 h after the end of treatment and were analysed for inositol trisphosphate (IP3). Neither acute nor chronic treatment aff ected basal levels of IP3 or stimulation of IP3 formation by either ca rbachol or noradrenaline in the hippocampus. Similarly, neither basal nor carbachol-stimulated IP3 levels in rat cortex were affected by acu te Li administration. It would appear that the reductions in these par ameters previously reported by other workers using brain slices were d ue to inositol depletion occurring at the stage of brain slice prepara tion. The inositol depletion hypothesis for the mechanism of action of lithium does not therefore appear to be supported by in vivo evidence .