Reversal of long-term methamphetamine sensitization by combination of pergolide with ondansetron or ketanserin, but not mirtazapine.
Reversal of long-term methamphetamine sensitization by combination of pergolide with ondansetron or ketanserin, but not mirtazapine.
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DOI：
10.1016/j.bbr.2011.04.045
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发表时间：
2011-09-30
影响因子：
2.7
通讯作者：
Lee, Tong H.
中科院分区：
文献类型：
--
作者：
Bhatia, Kamal S.;Szabo, Steven T.;Fowler, J. Corey;Wetsel, William C.;Lee, Tong H.
关键词：
精神兴奋剂滥用是一种精神疾病，是一种社会问题，在很大程度上不适合进行治疗干预。我们以前已经证明，5-HT 3拮抗剂昂丹司琼或非选择性5-HT 2A/2C拮抗剂酮色林给药后3.5小时，每日培高利特，非选择性DA激动剂，逆转先前建立的可卡因致敏。本研究旨在评估培高利特与抗抑郁药米氮平的相同治疗或延迟配对是否也可以逆转巩固的甲基苯丙胺（METH）行为致敏。Sprague-Dawley大鼠通过渗透微型泵接受METH输注（25 mg/kg/天，s.c.）持续7天，伴随每日注射递增的METH剂量（0-6 mg/kg，s.c.）。该方案考虑了大鼠中METH的更快消除，并设计为复制血浆METH浓度，并叠加人类METH暴饮暴食发作期间观察到的峰值药物水平。在7天的METH停药后，昂丹司琼（0.2mg/kg，s.c.），酮色林（1.0 mg/kg，s.c.），或米氮平（10 mg/kg，i. p.）在注射培高利特（0.1mg/kg，s.c.，qd）7天。在联合治疗停止后14天评估作为METH滥用模型的行为致敏（即，METH停药的第28天）通过用METH（0.5mg/kg，i. p.）急性攻击。培高利特联合昂丹司琼或酮色林可逆转METH行为敏化，但培高利特-米氮平联合无效。通过非选择性DA受体激动剂重新激活成瘾“回路”，随后通过5-HT 3或5-HT 2拮抗剂在逆转METH致敏和治疗METH成瘾中的再巩固阻断的作用进行了讨论。
Psychostimulant abuse represents a psychiatric disorder and societal concern that has been largely unamenable to therapeutic interventions. We have previously demonstrated that the 5-HT3 antagonist ondansetron or non-selective 5-HT2A/2C antagonist ketanserin administered 3.5 hours following daily pergolide, a non-selective DA agonist, reverses previously established cocaine sensitization. The present study was conducted to evaluate whether the same treatments or delayed pairing of pergolide with the antidepressant mirtazapine can also reverse consolidated methamphetamine (METH) behavioral sensitization. Sprague-Dawley rats received METH infusion via osmotic minipumps (25 mg/kg/day, s.c.) for 7 days, with accompanying daily injections of escalating METH doses (0–6 mg/kg, s.c.). This regimen takes into account the faster elimination of METH in rats, and is designed to replicate plasma METH concentrations with superimposed peak drug levels as observed during METH binging episodes in humans. Following a 7-day METH withdrawal, ondansetron (0.2 mg/kg, s.c.), ketanserin (1.0 mg/kg, s.c.), or mirtazapine (10 mg/kg, i.p.) was administered 3.5 hours after pergolide injections (0.1 mg/kg, s.c., qd) for 7 days. Behavioral sensitization as a model of METH abuse was assessed 14 days after the combination treatment cessation (i.e., day 28 of METH withdrawal) through an acute challenge with METH (0.5 mg/kg, i.p.). Pergolide combined with ondansetron or ketanserin reversed METH behavioral sensitization, but pergolide-mirtazapine combination was ineffective. The role of reactivation of addiction “circuit” by a non-selective DA agonist, and subsequent reconsolidation blockade through 5-HT3 or 5-HT2 antagonism in reversal of METH sensitization and treatment of METH addiction is discussed.
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影响因子：
5
作者：
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通讯作者：
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影响因子：
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