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

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Abstract
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 μg 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+. Morever, 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.