Effects of oral calcium dosage and timing on ethanol-induced sensitization of locomotion in DBA/2 mice

Abstract

Ethanol (EtOH) dosage, frequency, and paired associative learning affect the risk of alcoholism. Recently, Spanagel et al. reported that acamprosate calcium (Acam Ca) prescribed for alcoholism exerts an anti-relapse effect via Ca. Ca is contained in foods, sometimes consumed with alcohol. Therefore, we investigated the association among oral Ca ingestion, EtOH-induced locomotor sensitization, and plasma Ca levels on how to consume Ca for moderate drinking. We used DBA/2 CrSlc mice, and CaCl2 as water-soluble Ca salts. For pre-administration, elemental Ca (50, 75, 100, or 150mg/kg, per os (p.o.)) or water for control was administered 1h before EtOH (2g/kg, 20v/v (%) EtOH in saline) administration intraperitoneal (i.p.) for locomotor sensitization or for plasma Ca level changes. For post-administration, elemental Ca (100mg/kg) was administered 1h after EtOH. Moreover, we employed bepridil and the dopamine D1 antagonist, SCH-23390 to further examine the mechanism of EtOH-induced sensitization. The locomotor sensitization segmentalized for 300s had two peaks (0–90s and 180–300s). Pre-administration of Ca (50, 75, and 100mg/kg) significantly reduced the 0–90-s peak, selectively blocked by SCH-23390, but “non-dose dependently” as Ca 150mg/kg did not have this effect. Bepridil blocked the suppressive effect of pre-administration of Ca (100mg/kg). The effective pre-doses of Ca (50–100mg/kg) maintained plasma Ca basal levels against EtOH-induced decrease of Ca. On the contrary, post-administration of Ca inversely led to significant promotion of sensitization of both locomotor peaks. Oral Ca intake had diverse effects on EtOH-induced sensitization depending on Ca dosage and timing.