Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus.
Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus.
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DOI：
10.1016/j.biopsych.2009.07.026
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发表时间：
2010-01-01
影响因子：
10.6
通讯作者：
Heilig M
中科院分区：
文献类型：
--
作者：
Barr CS;Chen SA;Schwandt ML;Lindell SG;Sun H;Suomi SJ;Heilig M
人类μ阿片受体基因（OPRM 1）的非同义A118 G多态性对酒精奖励和纳洛酮治疗效果的作用仍有争议。恒河猴中功能等同的OPRM 1 C77 G多态性允许在受控实验条件下解决这一问题。对21只恒河猴（13只雌性，8只雄性）进行OPRM 1 C77 G基因分型，并在1小时的时间段内研究了在基线时间段中对加糖的酒精溶液（8.4%v/v）和非酒精对照液的偏好，然后在受试者内设计中进行了平衡的纳洛酮（1 mg/kg）和溶媒治疗。控制基线和性别的混合模型ANOVA显示基因型和治疗之间的相互作用非常显著（p=0.003）。事后分析显示，载体治疗的77 G携带者比77 C纯合子受试者具有显著更高的酒精偏好（p=0.001）。纳洛酮给药后，77 G携带者的偏好降低（p=0.002），与77 C纯合子受试者不再不同。相比之下，后一组不受治疗影响，事实上，在纳洛酮治疗后显示出偏好的趋势水平增加。这些结果支持OPRM 1变异对纳洛酮疗效的关键药物遗传学作用。
The role of a non-synonymous A118G polymorphism of the human mu-opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of naltrexone remains controversial. A functionally equivalent OPRM1 C77G polymorphism in rhesus macaques allows this to be addressed under controlled experimental conditions. Twenty one rhesus macaques (13 females, 8 males) were genotyped for OPRM1 C77G, and studied during 1h sessions for preference between an aspartame sweetened alcohol solution (8.4% v/v) and a non-alcoholic control fluid, in a baseline session followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced within-subject design. Mixed-model ANOVA controlling for baseline and sex showed a highly significant (p=0.003) interaction between genotype and treatment. Post-hoc analysis showed that vehicle treated 77G carriers had markedly higher alcohol preference than 77C homozygous subjects (p=0.001). Following naltrexone administration, 77G carriers decreased their preference (p=0.002), and no longer differed from 77C homozygous subjects. In contrast, the latter group was unaffected by treatment, and in fact showed a trend-level increase of preference following naltrexone. These results support a critical pharmacogenetic role of OPRM1 variation for therapeutic efficacy of naltrexone.
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影响因子：
10.6
作者：
Krishnan-Sarin, Suchitra;Krystal, John H.;O'Malley, Stephanie S.
通讯作者：
O'Malley, Stephanie S.
影响因子：
3.5
作者：
Shabalina SA;Zaykin DV;Gris P;Ogurtsov AY;Gauthier J;Shibata K;Tchivileva IE;Belfer I;Mishra B;Kiselycznyk C;Wallace MR;Staud R;Spiridonov NA;Max MB;Goldman D;Fillingim RB;Maixner W;Diatchenko L
通讯作者：
Diatchenko L
DOI：
10.1111/j.1530-0277.2007.00339.x
发表时间：
2007-04-01
影响因子：
3.2
作者：
Gelernter, Joel;Gueorguieva, Ralitza;Krystal, John H.
通讯作者：
Krystal, John H.
影响因子：
--
作者：
Anton, Raymond F.;Oroszi, Gabor;Goldman, David
通讯作者：
Goldman, David
影响因子：
--
作者：
Ray, Lara A.;Hutchison, Kent E.
通讯作者：
Hutchison, Kent E.