RT Journal Article SR Electronic T1 Effects of Acute and Chronic Barbiturate Administration on Synaptosomal Calcium Accumulation JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 386 OP 395 VO 15 IS 2 A1 MICHAEL G. ONDRUSEK A1 JOHN K. BELKNAP A1 STEVEN W. LESLIE YR 1979 UL http://molpharm.aspetjournals.org/content/15/2/386.abstract AB Synaptosomes were isolated from four treatment groups of DBA/2J mice: Group I-Control; Group II-7 day tolerant (received dietary phenobarbital, 2.5 mg/g Purina Lab Chow for 7 days); Group III-20 hr withdrawn; and Group IV-7 day recovered (received dietary phenobarbital for 7 days followed by normal diet for 7 days). Pentobarbital (0.45 mM) added in vitro to synaptosomes from control mice significantly depressed (21.4%) potassium depolarized 45Ca++ accumulation but did not significantly alter nondepolarized 45Ca++ uptake or subsequent 45Ca++ efflux. Chronic administration of phenobarbital to mice in the tolerant and withdrawn conditions resulted in behavioral tolerance and subsequent withdrawal symptomatology, but neither KCl-induced 45Ca++ accumulation nor 45Ca++ efflux was significantly altered. In vitro addition of pentobarbital (0.45 mM) to synaptosomes from tolerant mice did not significantly depress KCl-induced 45Ca++ accumulation (8.1%) but did significantly depress KCl-induced 45Ca++ accumulation by synaptosomes from withdrawn mice (15.2%) and recovered mice (16.8%). These data suggest that barbiturates may depress calcium-mediated stimulus-secretion coupling events contributing to central nervous system depression. Further, functional tolerance after chronic barbiturate treatment may result from a membrane adaptation facilitating calcium-mediated secretory functions.