The sensitizing effect of acute nicotine on amphetamine-stimulated behavior and dopamine efflux requires activation of β2 subunit-containing nicotinic acetylcholine receptors and glutamate N-methyl-D-aspartate receptors.
The sensitizing effect of acute nicotine on amphetamine-stimulated behavior and dopamine efflux requires activation of β2 subunit-containing nicotinic acetylcholine receptors and glutamate N-methyl-D-aspartate receptors.
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DOI：
10.1016/j.neuropharm.2010.10.003
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发表时间：
2011-06
影响因子：
4.7
通讯作者：
Gnegy, Margaret E.
中科院分区：
文献类型：
--
作者：
Kim, Myung N.;Jutkiewicz, Emily M.;Zhang, Minjia;Gnegy, Margaret E.
尼古丁已被证明会增强动物和人类对非法药物的后续使用。我们之前在雌性 Holtzman 大鼠中证明，1-4 小时后给予低剂量的 d-安非他明 (AMPH)，一剂低剂量的尼古丁会增强运动活性和多巴胺 (DA) 流出。在本研究中，我们表明这种情况也发生在雄性大鼠中，并描述了尼古丁对 AMPH 刺激的运动行为和 AMPH 诱导的 DA 流出快速敏化作用所需的受体。与盐水预处理相比，在用 AMPH（0.32 mg/kg，腹腔注射）攻击前 2-4 小时对雄性 Holtzman 大鼠进行低剂量（0.1 mg/kg，腹腔注射）尼古丁预处理可增强运动行为。二氢-β-赤霉素 (DHβE) 是含 β2 亚基 (β2*) 烟碱乙酰胆碱受体 (nAChR) 的相对选择性拮抗剂，但不是甲基利卡乌头碱 (MLA)（α7 nAChR 的相对选择性拮抗剂），可阻断尼古丁对 AMPH 刺激的运动活动的敏化作用。用伐尼克兰（一种对 β2* nAChR 选择性的部分激动剂）进行预处理，可阻断尼古丁对 AMPH 刺激的运动行为的敏化作用。与盐水预处理的大鼠相比，尼古丁预处理使腹侧（伏隔核，NAc）切片中 AMPH 诱导的 DA 溢出敏感，但对背侧纹状体不敏感。 DA 溢出的尼古丁敏化被 DHβE 阻断。在尼古丁前 30 分钟用谷氨酸 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂 (+)-MK801 (0.1 mg/kg, s.c.) 进行预处理，可阻断响应 AMPH 攻击的运动和 DA 溢出的敏化。这些结果表明，尼古丁对 AMPH 作用的快速敏化作用需要激活 β2* nAChR 和 NMDA 受体。
Nicotine has been demonstrated to enhance the subsequent use of illicit drugs in animals and humans. We previously demonstrated in female, Holtzman rats that one low dose of nicotine will potentiate locomotor activity and dopamine (DA) efflux in response to a subsequent low dose of d-amphetamine (AMPH) given 1-4 hours later. In the present study, we show this also occurs in male rats and characterize the receptors required for the rapid sensitizing effect of nicotine on AMPH-stimulated locomotor behavior and AMPH-induced DA efflux. Pretreatment of male, Holtzman rats with a low dose (0.1 mg/kg, i.p.) of nicotine 2-4 hours before a challenge with AMPH (0.32 mg/kg, i.p.) enhanced locomotor behavior as compared to saline pretreatment. Dihydro-β-erythroidine (DHβE), a relatively selective antagonist at β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChR), but not methyllycaconitine (MLA), a relatively selective antagonist at α7 nAChRs, blocked the sensitizing effect of nicotine on AMPH-stimulated locomotor activity. Pretreatment with varenicline, a partial agonist selective for β2* nAChRs, blocked the sensitizing effect of nicotine on AMPH-stimulated locomotor behavior. Nicotine pretreatment sensitized AMPH-induced DA overflow in slices from ventral (nucleus accumbens, NAc), but not dorsal striatum as compared to saline-pretreated rats. Nicotine sensitization of the DA overflow was blocked by DHβE. Pretreatment with the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK801 (0.1 mg/kg, s.c.) 30 min before nicotine blocked sensitization of both locomotion and DA overflow in response to AMPH challenge. These results demonstrate that activation of the β2* nAChRs and NMDA receptors are required for the rapid sensitizing effect of nicotine on AMPH actions.
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