Reduction of alcohol drinking and upregulation of opioid receptors by oral naltrexone in AA rats.
Reduction of alcohol drinking and upregulation of opioid receptors by oral naltrexone in AA rats.
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口服纳曲酮可减少 AA 大鼠的饮酒量并上调阿片受体。
DOI：
10.1016/s0741-8329(00)00091-4
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发表时间：
2000
期刊：
影响因子：
2.3
通讯作者：
J. Sinclair
中科院分区：
文献类型：
--
作者：
H. Parkes;J. Sinclair
高饮酒AA系大鼠在每天饮用10%乙醇前1h灌胃1 mg/kg纳曲酮(NTX)或无应激程序，连续8d，并在前7d 8h后再次灌胃纳曲酮(NTX)。治疗后1~4d，用0.03~6.00 nM[~3H]纳洛酮进行前脑组织匀浆结合实验。NTX显著抑制酒精摄入量，随着时间的推移，这种影响逐渐增强，并在治疗后持续。脑匀浆饱和结合实验显示，NTX治疗后第1天至第4天，阿片受体的Bmax分别增加93%、74%、49%和28%，而KD无改变。Bmax与前1小时饮酒量呈负相关(r=−0.510，p=0.008)，而对照组Bmax与随时间变化的饮酒量呈正相关(r=+0.790，p=0.020)。这些结果与阿片受体介导酒精强化以及NTX通过消退减少随后的饮酒的假设是一致的。阿片受体上调可与戒酒同时发生，并可能部分抵消NTX在治疗酒精中毒方面的临床益处。
Rats of the high-drinking AA line were given 1 mg/kg naltrexone (NTX) or vehicle orally with a stress-free procedure just before 1 h of access to 10% ethanol daily for 8 days and again, 8 h later on the first 7 days. Forebrain homogenate binding studies using 0.03–6.00 nM [3H] naloxone were conducted from 1 to 4 days following treatment. NTX significantly suppressed alcohol intake, with the effect becoming progressively greater over days and continuing during the post-treatment period. Saturation binding studies in brain homogenate revealed that NTX had increased the Bmaxfor opioid receptors by 93%, 74%, 49%, and 28%, respectively, from post-treatment days 1 to 4 without altering Kd. Bmaxwas negatively correlated (r=−0.510, p=0.008) with alcohol intake during the preceding hour, but in control rats, it was positively correlated with changes in alcohol intake over time (r=+0.790, p=0.020). These results are consistent with the hypothesis that opioid receptors mediate reinforcement from alcohol and that NTX reduces subsequent alcohol drinking by extinction. Opioid receptor upregulation can develop simultaneously with suppression of drinking and may partially counteract the clinical benefits from NTX in the treatment of alcoholism.
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纳曲酮诱导的阿片受体上调的神经化学和功能相关性。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Tempel,A;Gardner,EL;Zukin,RS
通讯作者：
Zukin,RS
影响因子：
--
作者：
O'Malley,SS;Jaffe,AJ;Chang,G;Schottenfeld,RS;Meyer,RE;Rounsaville,B
通讯作者：
Rounsaville,B
阿片受体亚型的上调与吗啡和 DADLE 的效力变化相关。
影响因子：
6.1
作者：
Yoburn,BC;Luke,MC;Pasternak,GW;Inturrisi,CE
通讯作者：
Inturrisi,CE
影响因子：
--
作者：
Volpicelli,JR;Alterman,AI;Hayashida,M;O'Brien,CP
通讯作者：
O'Brien,CP
影响因子：
5
作者：
Yoburn,BC;Sierra,V;Lutfy,K
通讯作者：
Lutfy,K