School of Behavioral and Brain Sciences, The University of Texas at Dallas, 800 West Campbell Rd, BSB14, Richardson, TX, 75080, USA.
Institute of Neurobiology, Jining Medical University, Jining, China.
Psychopharmacology (Berl). 2018 Jul;235(7):2027-2040. doi: 10.1007/s00213-018-4900-1. Epub 2018 Apr 20.
Acamprosate (calcium-bis N-acetylhomotaurinate) is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Acamprosate can improve executive functions that are impaired by chronic intermittent ethanol (CIE) exposure. Recent work has suggested that acamprosate's effects on relapse prevention are due to its calcium component, which raises the question whether its pro-cognitive effects are similarly mediated by calcium.
This study examined the effects of acamprosate on alcohol-induced behavioral deficits and compared them with the effects of the sodium salt version of N-acetylhomotaurinate or calcium chloride, respectively.
We exposed mice to alcohol via three cycles of CIE and measured changes in alcohol consumption in a limited-access paradigm. We then compared the effects of acamprosate and calcium chloride (applied subchronically for 3 days during withdrawal) in a battery of cognitive tasks that have been shown to be affected by chronic alcohol exposure.
CIE-treated animals showed deficits in attentional set-shifting and deficits in novel object recognition. Alcohol-treated animals showed no impairments in social novelty detection and interaction, or delayed spontaneous alternation. Both acamprosate and calcium chloride ameliorated alcohol-induced cognitive deficits to comparable extents. In contrast, the sodium salt version of N-acetylhomotaurinate did not reverse the cognitive deficits.
These results add evidence to the notion that acamprosate produces its anti-relapse effects through its calcium moiety. Our results also suggest that improved regulation of drug intake by acamprosate after withdrawal might at least in part be related to improved cognitive function.
钙-双 N-乙酰高牛磺酸（acamprosate）是一种被批准用于维持戒断的主要药物，已被证明可减少动物模型和人类酗酒者的渴望和复发。钙-双 N-乙酰高牛磺酸可改善因慢性间歇性乙醇（CIE）暴露而受损的执行功能。最近的研究表明，钙-双 N-乙酰高牛磺酸预防复发的作用归因于其钙成分，这引发了一个问题，即其促进认知的作用是否也同样由钙介导。
本研究检查了钙-双 N-乙酰高牛磺酸对酒精引起的行为缺陷的影响，并将其与 N-乙酰高牛磺酸的钠盐或氯化钙的影响进行了比较。
我们通过 CIE 的三个周期使小鼠接触酒精，并在有限接触的范式中测量酒精消耗量的变化。然后，我们在一系列认知任务中比较了钙-双 N-乙酰高牛磺酸和氯化钙（在戒断期间亚慢性应用 3 天）的影响，这些任务已被证明受慢性酒精暴露的影响。
CIE 处理的动物在注意力定势转移和新物体识别方面表现出缺陷。酒精处理的动物在社会新颖性检测和互动方面没有表现出缺陷，也没有表现出延迟的自发交替。钙-双 N-乙酰高牛磺酸和氯化钙都在相当程度上改善了酒精引起的认知缺陷。相比之下，N-乙酰高牛磺酸的钠盐版本没有逆转认知缺陷。
这些结果增加了钙-双 N-乙酰高牛磺酸通过其钙部分产生其抗复发作用的证据。我们的结果还表明，戒断后钙-双 N-乙酰高牛磺酸对药物摄入的调节改善可能至少部分与认知功能的改善有关。
