The effect of age and pentobarbitone tolerance on pentobarbitone depression of calcium-45 uptake by mouse brain synaptosomes.

Nerve terminals (synaptosomes) isolated from mouse brains accumulate 45Ca2+ at a rate which can be stimulated to increase by immersion in a high K+ saline. Low concentrations of pentobarbitone depress stimulated 45Ca2+ accumulation in a dose-dependent manner. We investigated the effect of 1 mM pentobarbitone on calcium accumulation by synaptosomes isolated from the brains of young and old mice, some of which had been made tolerant to barbiturates, to see if age and tolerance to barbiturate would modify 45Ca2+ accumulation. In the absence of barbiturate, neither advancing age nor barbiturate tolerance could be associated with any significant change in 45Ca2+ uptake by potassium-stimulated or non-stimulated synaptosomes. However, both factors modified the depressant effect of barbiturate. Age and tolerance did not influence resting or potassium-stimulated 45Ca2+ uptake, nor did they influence the suppression by pentobarbitone of resting 45Ca2+ uptake. However, when correcting for suppression of resting uptake by barbiturate, age significantly reduced barbiturate suppression of potassium-stimulated 45Ca2+ uptake. Tolerance significantly reduced this corrected effect of barbiturate in synaptosomes from the 3-month old but not the 24-month-old mice.