Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats.
Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats.
复制标题
DOI：
10.1371/journal.pone.0101807
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
LeSage MG
中科院分区：
文献类型：
--
作者：
Pravetoni M;Pentel PR;Potter DN;Chartoff EH;Tally L;LeSage MG
处方阿片类药物滥用是美国日益严重的公共卫生问题。包含与载体蛋白钥孔血蓝蛋白（OXY-KLH）缀合的半抗原（OXY）的疫苗已显示减弱羟考酮的抗伤害感受作用。在这里，疫苗的能力，以防止收购静脉内（i. v.）在大鼠中研究了羟考酮自身给药。还研究了接种疫苗对羟考酮诱导的中脑边缘系统内几种基因表达变化的影响，这些基因受慢性阿片类药物使用的调节。与用未缀合的KLH载体蛋白免疫的对照大鼠相比，用OXY-KLH接种降低了在固定比率（FR）3强化方案下获得羟考酮静脉内自我给药的大鼠的比例。在整个方案期间，疫苗接种显著减少了FR 3时的平均输注次数、输注总次数和羟考酮总摄入量。与单独用载体免疫的羟考酮自我给药对照大鼠相比，用OXY-KLH免疫原免疫的大鼠显示出纹状体中腺苷酸环化酶5（Adcy 5）水平增加和早期生长反应蛋白2（Egr 2）和早期直接基因c-Fos水平降低。这些数据表明，OXY-KLH疫苗接种可在临床相关暴露水平下减弱羟考酮的强化作用。mRNA表达分析确定了一些成瘾相关标志物，这些标志物可能对理解羟考酮的作用或疫苗接种提供的保护感兴趣。
Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY) conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH) has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v.) oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR) 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5) and decreased levels of early growth response protein 2 (Egr2) and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination.
登录
查看更多内容
影响因子：
7.3
作者：
Pravetoni, Marco;Le Naour, Morgan;Tucker, Ashli M.;Harmon, Theresa M.;Hawley, Tara M.;Portoghese, Philip S.;Pentel, Paul R.
通讯作者：
Pentel, Paul R.
影响因子：
3.6
作者：
Kuntz, Kara L.;Patel, Kruti M.;Vrana, Kent E.
通讯作者：
Vrana, Kent E.
影响因子：
3.4
作者：
Kantak, KN;Collins, SL;Fox, BS
通讯作者：
Fox, BS
影响因子：
4.5
作者：
Olesen, Anne E.;Upton, Richard;Drewes, Asbjorn M.
通讯作者：
Drewes, Asbjorn M.
影响因子：
3.7
作者：
Pravetoni, Marco;Vervacke, Jeffrey S.;Pentel, Paul R.
通讯作者：
Pentel, Paul R.