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 CaCl 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.

Influence of Housing Systems on Physical, Emotional, and Cognitive Functions with Aging in DBA/2CrSlc Mice

“…The DBA/2 strain rapidly develops a robust sensitization to ethanol compared to other strains. Previously, we have examined the rewarding degrees of moderate drinking using the conditioned place preference (CPP) test as well as the sensitization of locomotor activities [19,20], and then evaluated behaviors in DBA/2 mice with aging. The CPP test is one of the most commonly used tests to evaluate the degree of reward and addiction to drugs [21][22][23] and foods [24,25] such as oil and sugars.…”

“…However, many aging studies have considered some limited physiological changes at only a few time points within a certain period and presented limited data. DBA/2 mice were frequently used for reward-based tests in our previous experiments [19,20]. Therefore, the optimal conditions of various behavioral tests including physical, emotional, and cognitive tests with aging were investigated in DBA/2 mice.…”

Calcium Carbonate Attenuates Withdrawal and Reduces Craving: A Randomized Controlled Trial in Alcohol-Dependent Patients

“…Pradhan and colleagues [12] compared the effects of acamprosate and calcium chloride (applied subchronically for 3 days during withdrawal) in a battery of cognitive tasks in animals providing evidence that calcium is the active component of acamprosate [12]. Oral calcium intake in mice also showed different effects on ethanol-induced sensitization depending on calcium dosage and timing [13].…”