Multiple interacting neural systems are involved in sustaining nicotine reinforcement. We and others have shown that dopamine D₁ receptors and glutamate NMDA receptors both play important roles in nicotine reinforcement. Blockade of D₁ receptors with the antagonist SCH-23390 (0.02 mg/kg) both acutely and chronically significantly decreased nicotine self-administration in rats. Blockade of NMDA receptors (10 mg/kg) acutely with memantine significantly increased nicotine self-administration, but chronic blockade of NMDA receptors with memantine significantly decreased nicotine self-administration. The current study examined the interactions of acute and chronic administration of SCH-23390 and memantine on nicotine self-administration in female rats. Replicating earlier studies, acute and chronic SCH-23390 significantly decreased nicotine self-administration and memantine had a biphasic effect with acute administration increasing nicotine self-administration and chronic memantine showed a non-significant trend toward decreasing it. However, chronic interaction study showed that memantine significantly attenuated the decrease in nicotine self-administration caused by chronic SCH-23390. These studies provide important information that memantine attenuates the efficacy of D₁ antagonist SCH 23390 in reducing nicotine-self-administration. These two drugs do not appear to have mutually potentiating effects to aid tobacco cessation.

多个相互作用的神经系统参与维持尼古丁强化。我们和其他人已经证明，多巴胺 D ₁受体和谷氨酸NMDA 受体在尼古丁强化中都发挥着重要作用。用拮抗剂 SCH-23390 (0.02 mg/kg)阻断 D ₁受体可急性和长期显着降低大鼠的尼古丁自我给药量。用美金刚急性阻断 NMDA 受体（10 mg/kg）显着增加尼古丁自我给药，但用美金刚慢性阻断 NMDA 受体显着降低尼古丁自我给药。目前的研究检查了 SCH-23390 和美金刚的急性和慢性给药对雌性大鼠自我给药尼古丁的相互作用。重复早期的研究，急性和慢性 SCH-23390 显着减少尼古丁自我给药，美金刚具有双相效应，急性给药增加尼古丁自我给药，而慢性美金刚显示出不显着的减少尼古丁自我给药的趋势。然而，慢性相互作用研究表明，美金刚显着减弱了慢性 SCH-23390 引起的尼古丁自我给药的减少。_{这些研究提供了重要信息，即美金刚会减弱 D 1}拮抗剂 SCH 23390 在减少尼古丁自我给药方面的功效。这两种药物似乎没有相互增强的帮助戒烟的作用。