Effects of Oral Calcium Dosage and Timing on Ethanol-Induced Sensitization of Locomotion in DBA/2 Mice

• Published in: Biological & pharmaceutical bulletin Vol. 41; no. 7; pp. 1049 - 1061
• Main Authors: Shimizu, Chikako, Mitani, Yutaka, Tsuchiya, Youichi, Nabeshima, Toshitaka
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.07.2018; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: acamprosate calcium; Alcoholism; Alcohols; Associative learning; bepridil; Calcium; Calcium chloride; dopamine antagonist; Dopamine D1 receptors; Dosage; Drinking behavior; Drug abuse; Ethanol; Ingestion; Locomotion; Salts; dopamine antagonist; bepridil; ethanol; Alcoholism; acamprosate calcium
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00093

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 150 mg/kg, per os (p.o.)) or water for control was administered 1 h before EtOH (2 g/kg, 20 v/v (%) EtOH in saline) administration intraperitoneal (i.p.) for locomotor sensitization or for plasma Ca level changes. For post-administration, elemental Ca (100 mg/kg) was administered 1 h 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 300 s had two peaks (0–90 s and 180–300 s). Pre-administration of Ca (50, 75, and 100 mg/kg) significantly reduced the 0–90-s peak, selectively blocked by SCH-23390, but “non-dose dependently” as Ca 150 mg/kg did not have this effect. Bepridil blocked the suppressive effect of pre-administration of Ca (100 mg/kg). The effective pre-doses of Ca (50–100 mg/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.