Regional calcium levels in rat and mouse brain: automated fluorimetric assay and effects of centrally acting drugs.

The effects of several drugs and other treatments on the regional levels of Ca2+ in the brain of mice and rats were determined with an automated assay, based on the formation of a fluorescent calcein complex in a continuous flow system. The method is linear (between 1.5 and 5 micrograms Ca2+ ml-1), specific (no other cations present in the brain showed fluorescence) and sensitive (10-100 mg brain tissue can be analyzed). No major effects with the following drugs, given once or repeatedly to mice at high doses were found: morphine, naloxone, haloperidol, sulpiride, chlordiazepoxide, reserpine, ethanol, mercaptopropionic acid, or pentobarbital. Cold stress produced a transient increase in the regional levels of Ca2+ in the mouse brain. Lithium sulphate produced a small increase of brain Ca2+ 24 h after a high and toxic dose. Sleep deprivation for 24 h was ineffective in these experiments. Local application of kainic acid and tetrodotoxine to the rat striatum had no acute effects, but kainic acid produced a five to tenfold increase in the levels of striatal Ca2+ 2 weeks after injection. The present study does not support earlier published findings, which suggested that several behaviourally active drugs produce significant decreases of brain Ca2+. Moreover, it provides no evidence that the several therapeutic treatments that resulted in changes in body fluid Ca2+ also alter cerebral levels of Ca2+. On the other hand, the present data do suggest that damage to nervous tissue substantially influences Ca2+ metabolism.