PT - JOURNAL ARTICLE AU - MICHAEL G. ONDRUSEK AU - JOHN K. BELKNAP AU - STEVEN W. LESLIE TI - Effects of Acute and Chronic Barbiturate Administration on Synaptosomal Calcium Accumulation DP - 1979 Mar 01 TA - Molecular Pharmacology PG - 386--395 VI - 15 IP - 2 4099 - http://molpharm.aspetjournals.org/content/15/2/386.short 4100 - http://molpharm.aspetjournals.org/content/15/2/386.full SO - Mol Pharmacol1979 Mar 01; 15 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Group II-7 day tolerant (received dietary phenobarbital, 2.5 mg/g Purina Lab Chow for 7 days); Group III-20 hr withdrawn; and Group IV-7 day recovered (received dietary phenobarbital for 7 days followed by normal diet for 7 days).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 Chronic administration of phenobarbital to mice in the tolerant and withdrawn conditions resulted in behavioral tolerance and subsequent withdrawal symptomatology, but neither KCl-induced 45Ca++ accumulation nor 45Ca++ efflux was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45Ca++ accumulation (8.1%) but did significantly depress KCl-induced 45Ca++ accumulation by synaptosomes from withdrawn mice (15.2%) and recovered mice (16.8%).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.