Gajbhiye Snehalata V, Tripathi Raakhi K, Salve Bharat, Petare Anup, Potey Anirudha V
Department of Pharmacology & Therapeutics, Seth GS Medical College & KEM Hospital, Mumbai, India.
Department of Pharmacology & Therapeutics, Seth GS Medical College & KEM Hospital, Mumbai, India.
Neurosci Lett. 2017 May 10;649:28-33. doi: 10.1016/j.neulet.2017.04.007. Epub 2017 Apr 10.
Medical management for alcohol abuse has limitations. Alcohol consumption activates N-methyl-d-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice.
To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone - 1mg/kg (positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17).
The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p<0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP.
Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse.
酒精滥用的药物治疗存在局限性。酒精消费会激活N-甲基-D-天冬氨酸受体并释放一氧化氮，而米诺环素可以抑制这种作用，因为它很容易穿过血脑屏障，并且可能对酒精消费产生影响。因此，本研究的目的是在小鼠条件性位置偏爱（CPP）模型中评估米诺环素对酒精诱导的奖赏特性、消退和复发现象的影响。
为了评估酒精的奖赏作用，CPP程序包括4个部分，连续11天进行，包括适应期（第1天）、预处理测试（第2天）、酒精（第3、5、7和9天）或生理盐水（第4、6、8和10天）条件化以及条件化后测试（第11天）。所设组包括生理盐水处理组（酒精对照组）、纳曲酮-1mg/kg（阳性对照组）以及剂量为10、30和50mg/kg的米诺环素组。为了评估米诺环素对酒精复发的影响，CPP程序包括6个部分，前4个与上述相同，随后是消退期（第12 - 16天）和复燃期（第17天）。
不同组在酒精配对隔室中花费的时间表明，与酒精对照组相比，米诺环素和纳曲酮显著减弱了酒精诱导的位置偏爱（p<0.05）。米诺环素和纳曲酮预处理可阻断消退的CPP的复燃。
米诺环素可能在减弱酒精的奖赏特性和预防酒精复发方面发挥作用。
