Intravenous self-administration of entactogen-class stimulants in male rats.
Intravenous self-administration of entactogen-class stimulants in male rats.
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雄性大鼠静脉内自行注射内生剂类兴奋剂。
DOI：
10.1016/j.neuropharm.2015.08.030
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发表时间：
2015
影响因子：
4.7
通讯作者：
Taffe,MichaelA
中科院分区：
文献类型：
--
作者：
Vandewater,SophiaA;Creehan,KevinM;Taffe,MichaelA
3,4-亚甲二氧基甲基苯丙胺 (MDMA) 的静脉自我给药 (IVSA) 在大鼠中的表现不一致，多达一半的受试者未能获得可靠的药物摄入量。目前尚不清楚这种情况在可卡因和甲基苯丙胺的 IVSA 升级的长时间接触条件（6 小时会话）下是否会发生变化。内生类卡西酮兴奋剂在伏核中表现出类似 MDMA 的单胺作用，甲麻黄酮（4-甲基甲卡西酮）和甲基酮（3,4-亚甲二氧基甲卡西酮）可能支持更可靠的 IVSA，但结果好坏参半。本研究旨在直接比较这三种化合物的 IVSA。雄性 Wistar 大鼠组接受训练，按照固定比例 (FR) 1 强化方案自行施用甲氧麻黄酮、甲基酮或 MDMA (0.5 mg/kg/inf)，共 14 次。采集间隔后，对动物进行 FR（0.0、0.125、0.25、0.5、1.0、2.5 mg/kg/inf）和进展比（PR；0.125、1.0 mg/kg/inf）剂量替代程序的评估。长时间访问条件会在 6 小时内增加 MDMA 摄入量，但在前 2 小时内不会增加。在短期访问中，在获得过程中，与甲基酮训练组或 MDMA 训练组相比，接受甲氧麻黄酮训练的大鼠的药物摄入量显着更高。在 MDMA 和甲麻黄酮训练组中，在 FR 和 PR 剂量替代期间，甲麻黄酮的摄入量最高。总体而言，研究发现甲氧麻黄酮是比甲基酮或摇头丸更有效的强化剂，并且代表着更高的强迫使用风险。
The intravenous self-administration (IVSA) of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in rats, with up to half of subjects failing to acquire reliable drug intake. It is unknown if this changes under long-access conditions (6 h sessions) under which the IVSA of cocaine and methamphetamine escalates. The entactogen class cathinone stimulants which exhibit MDMA-like monoamine effects in the nucleus accumbens, mephedrone (4-methylmethcathinone) and methylone (3,4-methylenedioxymethcathinone), may support more reliable IVSA but results have been mixed. This study was designed to directly compare the IVSA of these three compounds. Groups of male Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and Progressive Ratio (PR; 0.125, 1.0 mg/kg/inf) dose-substitution procedures. Long access conditions escalated MDMA intake over the 6 h session but not in the first 2 h. In short access, drug intake was significantly higher in mephedrone-trained rats compared with either the methylone-trained or MDMA-trained groups during acquisition. Mephedrone resulted in the highest intakes during FR and PR dose-substitution in MDMA- and mephedrone-trained groups. Overall it was found that mephedrone is a more effective reinforcer than methylone or MDMA and represents a higher risk for compulsive use.