Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine.
Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine.
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DOI：
10.1007/s00213-020-05558-0
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发表时间：
2020-09
影响因子：
3.4
通讯作者：
Fantegrossi WE
中科院分区：
文献类型：
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作者：
McClenahan SJ;Gunnell MG;Owens SM;Fantegrossi WE
3,4-亚甲基二氧基丙戊酮（MDPV）是一种合成卡西酮，因其在“浴盐”产品中具有类似可卡因的精神兴奋剂作用而被滥用。虽然目前还没有针对MDPV滥用的药物治疗方法，但啮齿动物研究表明免疫疗法可能是一种可行的治疗选择。这些研究在Sprague-Dawley大鼠中测试了主动接种疫苗减少MDPV强化作用的能力。大鼠按照FR1计划获得可卡因自我给药（0.32 mg/kg/inf）。可卡因（0.032 - 1.0 mg/kg/inf）和MDPV （0.001 - 0.32 mg/kg/inf）的剂量效应函数是根据FR5表确定的。疫苗组大鼠在可卡因自我给药期间免疫。所有大鼠都过渡到递进比例（PR）计划，以建立可卡因（0.1 - 1.0 mg/kg/inf）和MDPV （0.01 - 0.32 mg/kg/inf）的断点。反应消失，评估线索诱导恢复和mdpv启动恢复（0.56 mg/kg， IP）。各组间可卡因自我给药的终点无差异，但对照组MDPV自我给药的ED50明显低于接种疫苗的大鼠。在PR计划下，MDPV在维持应答方面比接种疫苗的大鼠强2.5倍，但Emax在组间没有差异。疫苗接种并没有减少mdpv引发的恢复，可能是由于抗体滴度的降低。疫苗接种没有改变可卡因自我给药的获得性，这表明了药理学选择性，并表明疫苗不影响学习或动机，同时有效地降低了MDPV作为强化剂的效力。疫苗的保护作用被大单位剂量的MDPV所超越，这表明药物结合疫苗在药物滥用障碍中的最大功效可能需要同时进行行为矫正治疗。
3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone abused for its cocaine-like psychostimulant effects in “bath salts” products. While there are currently no pharmacotherapies for MDPV abuse, rodent studies suggest immunotherapy may offer a feasible treatment option. These studies tested the capacity of active vaccination to reduce the reinforcing effects of MDPV in Sprague-Dawley rats. Rats acquired cocaine self-administration (0.32 mg/kg/inf) on an FR1 schedule. Dose-effect functions for cocaine (0.032 – 1.0 mg/kg/inf) and MDPV (0.001 – 0.32 mg/kg/inf) were determined under an FR5 schedule. Rats in the vaccine group were immunized during cocaine self-administration. All rats transitioned to a progressive ratio (PR) schedule to establish breakpoints for cocaine (0.1 – 1.0 mg/kg/inf) and MDPV (0.01 – 0.32 mg/kg/inf)., Responding was extinguished, and cue-induced and MDPV-primed reinstatement (0.56 mg/kg, IP) were evaluated. No endpoints of cocaine self-administration differed between groups, but the ED50 for MDPV self-administration was significantly lower in control relative to vaccinated rats. Under the PR schedule, MDPV was ~2.5-fold more potent in maintaining responding in control than vaccinated rats, but Emax was not different between groups. Vaccination did not reduce MDPV-primed reinstatement, perhaps due to a decrease in antibody titer. Vaccination did not alter acquisition of cocaine self-administration, demonstrating pharmacological selectivity and suggesting that the vaccine did not affect learning or motivation, while effectively reducing the potency of MDPV as a reinforcer. The protective effects of the vaccine were surmounted by large unit doses of MDPV, suggesting maximal efficacy of drug-conjugate vaccines in substance abuse disorders will likely require concurrent behavior modification therapy.
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影响因子：
3.4
作者：
Watterson LR;Kufahl PR;Nemirovsky NE;Sewalia K;Grabenauer M;Thomas BF;Marusich JA;Wegner S;Olive MF
通讯作者：
Olive MF
影响因子：
5.5
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
通讯作者：
Owens, S. Michael
影响因子：
--
作者：
Watterson, Lucas R;Kufahl, Peter R;Olive, M Foster
通讯作者：
Olive, M Foster
DOI：
10.1124/jpet.116.239376
发表时间：
2017-04-01
影响因子：
3.5
作者：
Gannon, Brenda M.;Galindo, Kayla I.;Collins, Gregory T.
通讯作者：
Collins, Gregory T.
影响因子：
10.6
作者：
Miller, Michelle L.;Moreno, Amira Y.;Aarde, Shawn M.;Creehan, Kevin M.;Vandewater, Sophia A.;Vaillancourt, Brittani D.;Wright, M. Jerry, Jr.;Janda, Kim D.;Taffe, Michael A.
通讯作者：
Taffe, Michael A.