Acute and chronic effects of methamphetamine on tele-methylhistamine levels in mouse brain:: Selective involvement of the D2 and not D3 receptor
Acute and chronic effects of methamphetamine on tele-methylhistamine levels in mouse brain:: Selective involvement of the D2 and not D3 receptor
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DOI：
10.1124/jpet.300.2.621
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发表时间：
2002-02-01
影响因子：
3.5
通讯作者：
Arrang, JM
中科院分区：
文献类型：
--
作者：
Morisset, S;Pilon, C;Arrang, JM
我们探索了内源性多巴胺在控制小鼠脑区组胺能神经元活性中的作用，通过端甲基组胺(t-MEHA)水平的变化来评估。在体外，甲基苯丙胺释放[H-3]去甲肾上腺素，但不能从突触体内释放[H-3]组胺。在体内，甲基苯丙胺使尾壳核、伏隔核、大脑皮层和下丘脑的t-MEHA水平增加约2倍，ED50值接近1 mg/kg。这种反应选择性地涉及D-2，而不是D-3受体，如氟哌啶醇阻断和给予D-3受体优先配体奈法多曲德或(-/-)D-3受体缺陷小鼠的持续所表明的那样。与这种药物的运动激活作用相比，t-MeHA对甲基苯丙胺的反应延迟，表明它具有代偿性质。与之一致的是，已知能增强组胺神经元活性的反向激动剂西普罗昔芬，减少了甲基苯丙胺引起的过度运动。重复给予甲基苯丙胺导致对药物的过度运动效应的预期增敏，但没有改变关于t-MeHA水平的ED50或E-max。然而，它导致基础t-MeHA水平升高(+30-40%)，在停药后下丘脑、纹状体和大脑皮质持续至少11天，并被氟哌啶醇抑制。因此，急性和长期服用甲基苯丙胺都会增强组胺神经元的活性，可能是以一种代偿的方式。重复给予甲基苯丙胺也改变了多巴胺和5-羟色胺对组胺能神经元的相反影响的平衡，分别表现为对氟哌啶醇的增强反应和对酮丝氨酸的抑制反应。
We have explored the role of endogenous dopamine in the control of histaminergic neuron activity in mouse brain regions evaluated by changes in tele-methylhistamine (t-MeHA) levels. In vitro, methamphetamine released [H-3]noradrenaline but failed to release [H-3]histamine from synaptosomes. In vivo, methamphetamine enhanced t-MeHA levels by about 2-fold with ED50 values of similar to1 mg/kg in caudate putamen, nucleus accumbens, cerebral cortex, and hypothalamus. This response selectively involved the D-2 and not the D-3 receptor as indicated by its blockade by haloperidol and by its persistence after administration of nafadotride, a D-3 receptor preferential ligand, or in (-/-) D-3 receptor-deficient mice. The t-MeHA response to methamphetamine was delayed compared with the locomotor-activating effect of this drug, suggesting that it is of compensatory nature. In agreement, ciproxifan, an inverse agonist known to enhance histamine neuron activity, decreased the hyperlocomotion induced by methamphetamine. Repeated methamphetamine administration resulted in the expected sensitization to the hyperlocomotor effect of the drug but did not modify either the ED50 or the E-max regarding t-MeHA levels. However, it resulted in an enhanced basal t-MeHA level (+30-40%), which was sustained for at least 11 days after withdrawal in hypothalamus, striatum, and cerebral cortex and suppressed by haloperidol. Hence, both the acute and chronic administration of methamphetamine enhance histamine neuron activity, presumably in a compensatory manner. Repeated methamphetamine administration also resulted in a modified balance in the opposite influences of dopamine and serotonin on histaminergic neurons as revealed by the enhanced response to haloperidol and abolished response to ketanserin, respectively.