Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food.
Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food.
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DOI：
10.1016/j.vaccine.2013.07.038
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发表时间：
2013-09-23
期刊：
影响因子：
5.5
通讯作者：
Owens, S. Michael
中科院分区：
文献类型：
--
作者：
Rueedi-Bettschen, Daniela;Wood, Sherri L.;Gunnell, Melinda G.;West, C. Michael;Pidaparthi, Rama R.;Carroll, F. Ivy;Blough, Bruce E.;Owens, S. Michael
（+）-甲基苯丙胺（METH）成瘾是一种慢性疾病，干扰基本的大脑介导的行为和生物功能，如进食。这些研究提供了用于治疗METH滥用的METH结合疫苗（ICKLH-SMO 9）的临床前有效性和安全性。ICKLH-SMO 9的功效和安全性在16周的时间内通过监测一般健康和食物维持行为范例中的响应稳定性来评估。训练雄性Sprague-Dawley大鼠用杠杆按压食物，直到建立稳定的行为。然后用100 μg在佐剂中的对照抗原载体蛋白（ICKLH-Cys）或ICKLH-SMO 9免疫大鼠（n=9/组），在4、8和12周进行加强免疫。每天评估健康、免疫部位和行为。在第14-16周期间，当抗体滴度和METH亲和力（Kd = 13.9 ± 1.7 nM）最大时，所有大鼠每3-4天接受逐渐增加的METH剂量（0.3-3.0 mg/kg），随后进行行为测试。即使0.3-1.0 mg/kg的较低METH剂量对食物维持行为没有损害，但3.0-mg/kg的对照大鼠显示出显著（p<0.05）降低的反应率和获得的食物数量，以及减少的食物摄入。与此形成鲜明对比的是，ICKLH-SMO 9组在任何METH剂量下均未显示出食物维持行为的变化，尽管由于抗METH抗体结合，METH血清浓度显示出显著增加。这些发现表明，ICKLH-SMO 9疫苗在减少不良METH诱导效应方面是有效和安全的，即使在高剂量METH下也是如此。
(+)-Methamphetamine (METH) addiction is a chronic disease that interferes with fundamental brain-mediated behaviors and biological functions like eating. These studies present preclinical efficacy and safety profiles for a METH conjugate vaccine (ICKLH-SMO9) designed to treat METH abuse. ICKLH-SMO9 efficacy and safety were assessed over a 16-week period by monitoring general health and stability of responding in a food maintained behavioral paradigm. Male Sprague-Dawley rats were trained to lever press for food reinforcers until stable behavior was established. Rats (n=9/group) were then immunized with 100 µg of a control antigenic carrier protein (ICKLH-Cys) or ICKLH-SMO9 in Alhydrogel® adjuvant, with booster immunizations at 4, 8 and 12 weeks. Health, immunization site and behavior were assessed daily. No adverse effects were found. During weeks 14–16, when antibody titers and METH affinity (Kd = 13.9 ± 1.7 nM) were maximal, all rats received progressively higher METH doses (0.3–3.0 mg/kg) every 3–4 days, followed by behavioral testing. Even though the lower METH doses from 0.3-1.0 mg/kg produced no impairment in food maintained behavior, 3.0-mg/kg in control rats showed significantly (p<0.05) reduced response rates and number of reinforcers earned, as well as reduced food intake. In sharp contrast, the ICKLH-SMO9 group showed no changes in food maintained behavior at any METH dose, even though METH serum concentrations showed profound increases due to anti-METH antibody binding. These findings suggest the ICKLH-SMO9 vaccine is effective and safe at reducing adverse METH-induced effects, even at high METH doses.
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影响因子：
7.3
作者：
Carroll FI;Abraham P;Gong PK;Pidaparthi RR;Blough BE;Che Y;Hampton A;Gunnell M;Lay JO Jr;Peterson EC;Owens SM
通讯作者：
Owens SM
影响因子：
56.9
作者：
CHO, AK
通讯作者：
CHO, AK
影响因子：
4.5
作者：
Hendrickson, Howard;Laurenzana, Elizabeth;Owens, S. Michael
通讯作者：
Owens, S. Michael
影响因子：
3.4
作者：
Kantak, KN;Collins, SL;Fox, BS
通讯作者：
Fox, BS
影响因子：
3.6
作者：
Milesi-Halle, Alessandra;McMillan, Donald E.;Owens, S. Michael
通讯作者：
Owens, S. Michael