Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV).
Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV).
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DOI：
10.1111/j.1369-1600.2012.00474.x
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发表时间：
2014-03
影响因子：
3.4
通讯作者：
Olive MF
中科院分区：
文献类型：
--
作者：
Watterson LR;Kufahl PR;Nemirovsky NE;Sewalia K;Grabenauer M;Thomas BF;Marusich JA;Wegner S;Olive MF
近年来，有关合成卡西酮滥用和毒性影响的报道急剧增加。合成卡西酮经常被当作“浴盐”或“法定高点”出售。3，4-亚甲基二氧基吡喃丙酮(MDPV)是应用最广泛的合成卡西酮之一。目前的研究通过评估MDPV对大鼠静脉自我给药的支持能力和降低大鼠颅内自我刺激(ICSS)的阈值来评估MDPV的滥用潜力。在第一个实验中，训练大鼠以0.05、0.1或0.2 mg/kg/次的剂量静脉注射MDPV，每天2小时，连续10天。然后允许大鼠在累进比率(PR)强化计划下自我给药MDPV。接下来，大鼠在短时间(2小时/天，SHA)或长时间(6小时/天，LGA)的接触条件下，自我给予MDPV 10天，以评估摄入量的增加。单独组大鼠除自身注射甲基苯丙胺(0.05 mg/kg/次)代替MDPV外，其余步骤相同。在第二个实验中，研究了急性给药(0.1、0.5、1和2 mg/kg i.p.)后MDPV对ICSS阈值的影响。都进行了评估。在测试的所有剂量中，MDPV保持自我给药。在PR条件下，MDPV剂量与增强断裂点呈正相关。在LGA条件下，0.1和0.2 mg/kg剂量的药物摄入量上升，而自行服用甲基苯丙胺的大鼠表现出类似的上升模式。最后，在测试的所有剂量下，MDPV显著降低了ICSS阈值。综上所述，这些发现表明，MDPV具有增强特性并激活大脑奖励电路，这表明人类可能会滥用和上瘾。
Reports of abuse and toxic effects of synthetic cathinones, frequently sold as “bath salts” or “legal highs”, have increased dramatically in recent years. One of the most widely used synthetic cathinones is 3,4-methylenedioxypyrovalerone (MDPV). The current study evaluated the abuse potential of MDPV by assessing its ability to support intravenous self-administration and lower thresholds for intracranial self-stimulation (ICSS) in rats. In the first experiment, rats were trained to intravenously self-administer MDPV in daily 2 hr sessions for 10 days at doses of 0.05, 0.1, or 0.2 mg/kg/infusion. Rats were then allowed to self-administer MDPV under a progressive ratio (PR) schedule of reinforcement. Next, rats self-administered MDPV for an additional 10 days under short (2 hr/day, ShA) or long (6 hr/day, LgA) access conditions to assess escalation of intake. Aseparate group of rats underwent the same procedures with the exception of self-administering methamphetamine (0.05 mg/kg/infusion) instead of MDPV. In a second experiment, the effects of MDPV on ICSS thresholds following acute administration (0.1, 0.5, 1 and 2 mg/kg i.p.) were assessed. MDPV maintained self-administration across all doses tested. A positive relationship between MDPV dose and breakpoints for reinforcement under PR conditions was observed. LgA conditions led to escalation of drug intake at the 0.1 and 0.2 mg/kg doses, and rats self-administering methamphetamine showed similar patterns of escalation. Finally, MDPV significantly lowered ICSS thresholds at all doses tested. Together, these findings indicate that MDPV has reinforcing properties and activates brain reward circuitry, suggesting a potential for abuse and addiction in humans.
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影响因子：
3.4
作者：
Gipson, Cassandra D.;Bardo, Michael T.
通讯作者：
Bardo, Michael T.
DOI：
10.1007/978-1-60761-934-5_2
发表时间：
2011-01-01
期刊：
ANIMAL MODELS OF DRUG ADDICTION
影响因子：
--
作者：
Panlilio, Leigh V.
通讯作者：
Panlilio, Leigh V.
DOI：
10.1007/bf00404009
发表时间：
1964-01-01
期刊：
PSYCHOPHARMACOLOGIA
影响因子：
--
作者：
HOLLIDAY, AR;MORRIS, RB;SHARPLEY, RP
通讯作者：
SHARPLEY, RP
影响因子：
3.6
作者：
MEISCH, RA
通讯作者：
MEISCH, RA
影响因子：
3.4
作者：
Kitamura, O;Wee, S;Pulvirenti, L
通讯作者：
Pulvirenti, L