The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release.
The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release.
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DOI：
10.1016/j.bbi.2009.01.014
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发表时间：
2009-05
影响因子：
15.1
通讯作者：
Johnson, Kirk W.
中科院分区：
文献类型：
--
作者：
Bland, Sondra T.;Hutchinson, Mark R.;Maier, Steven F.;Watkins, Linda R.;Johnson, Kirk W.
神经胶质细胞的激活最近被发现可以调节吗啡的几种作用，包括镇痛、耐受性和依赖性。目前的研究通过探索神经胶质激活是否也可能影响伏隔核（NAc）壳中多巴胺（DA）的细胞外水平，这是吗啡诱导药物奖励的神经化学必然结果，在有或没有沉淀戒断的实验中，在吗啡的挑战剂量期间。吗啡或对照物静服4天（起始剂量为15mg /kg/天至20mg /kg/天），神经胶质活化抑制剂AV411 （7.5 mg/kg）或对照物每日两次。然后在透析期间给予吗啡（22.5 mg/kg）或生理盐水激发剂量。在第一个实验中，AV411或载药治疗的大鼠在透析1小时后给予纳洛酮（10 mg/kg），并在微透析期间评估躯体戒断的行为体征。在第二个实验中，使用相同的给药方案，在吗啡或生理盐水后，AV411或载药处理的大鼠继续取样3小时。纳洛酮治疗前，药组大鼠NAc DA明显高于av411治疗大鼠，av411治疗大鼠戒断症状明显减轻。AV411对吗啡诱导的NAc - DA的降低是持续性的，持续3小时以上。这些结果表明，神经胶质激活有助于吗啡对NAc - DA的影响，而NAc - DA与沉淀戒断的躯体体征有关。
Glial activation has recently been discovered to modulate several effects of morphine, including analgesia, tolerance, and dependence. The present studies extend this line of investigation by exploring whether glial activation may also affect extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) shell, a neurochemical corollary of morphine-induced drug reward, during a challenge dose of morphine in experiments both with and without precipitated withdrawal. Morphine or vehicle was administered s.c. for 4 days (starting at 15 mg/kg/day up to 20 mg/kg/day), and the glial activation inhibitor AV411 (7.5 mg/kg) or vehicle was administered twice daily. A challenge dose of morphine (22.5 mg/kg) or saline was then given during dialysis. In the first experiment, naloxone (10 mg/kg) was administered 1 hr after morphine during dialysis in AV411- or vehicle-treated rats, and behavioral signs of somatic withdrawal were assessed during microdialysis. In the second experiment, using the same dosing regimen, sampling continued 3 hr after morphine or saline in AV411- or vehicle-treated rats. NAc DA increased in vehicle-treated rats significantly more than in AV411-treated rats before naloxone treatment, and withdrawal symptoms were significantly reduced in AV411-treated rats. The decrease in morphine-induced NAc DA by AV411 was persistent, lasting 3+ hr post-morphine. These results indicate that glial activation contributes to the effects of morphine on NAc DA, which is associated with somatic signs of precipitated withdrawal.
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影响因子：
5
作者：
Gholami, A;Zarrindast, MR;Haerri-Rohani, A
通讯作者：
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影响因子：
3.4
作者：
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DOI：
10.1358/mf.1998.20.7.485728
发表时间：
1998-09-01
影响因子：
--
作者：
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通讯作者：
Nabeshima, T
影响因子：
5.8
作者：
Madelian, V;LaVigne, E
通讯作者：
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影响因子：
15.1
作者：
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通讯作者：
Przewlocka, Barbara