TY - JOUR
T1 - Effects of oral calcium dosage and timing on ethanol-induced sensitization of locomotion in DBA/2 mice
AU - Shimizu, Chikako
AU - Mitani, Yutaka
AU - Tsuchiya, Youichi
AU - Nabeshima, Toshitaka
N1 - Publisher Copyright:
© 2018 The Pharmaceutical Society of Japan.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85049366448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049366448&partnerID=8YFLogxK
U2 - 10.1248/bpb.b18-00093
DO - 10.1248/bpb.b18-00093
M3 - Article
C2 - 29769465
AN - SCOPUS:85049366448
SN - 0918-6158
VL - 41
SP - 1049
EP - 1061
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 7
ER -