Responses of limbic and extrapyramidal substance P systems to nicotine treatment
Responses of limbic and extrapyramidal substance P systems to nicotine treatment
复制标题
DOI：
10.1007/s00213-008-1316-3
复制
发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Hanson, Glen R.
中科院分区：
文献类型：
--
作者：
Alburges, Mario E.;Frankel, Paul S.;Hanson, Glen R.
神经肽主要通过多巴胺机制与滥用兴奋剂的精神病理学有关。 P 物质 (SP) 是这些神经肽之一，与边缘和锥体外系多巴胺能通路相关，并且可能有助于这些兴奋剂的药理学。尼古丁对这些多巴胺系统的影响也得到了广泛的研究。在本研究中，我们通过测量相关 SP 组织浓度的变化来阐明尼古丁治疗对边缘和锥体外系 SP 系统的影响。雄性 Sprague-Dawley 大鼠在存在或不存在选择性多巴胺 D-1 和D-2 受体拮抗剂或非选择性烟碱乙酰胆碱受体拮抗剂。尼古丁治疗显着但暂时降低了药物暴露后 12-18 小时腹侧被盖区 (VTA) 和黑质中 P 物质样免疫反应性 (SPLI) 的含量。美加明以及多巴胺 D-1、D-2 或两种受体拮抗剂预处理可选择性阻断尼古丁介导的 SPLI 变化。其他大脑区域也选择性地表现出与尼古丁相关的 SPLI 含量下降，包括前额皮质、伏核壳和尾状核。这些发现表明，一些边缘和基底神经节 SP 系统通过尼古丁和多巴胺能受体介导的过程受到尼古丁暴露的显着影响，表明 SP 途径在尼古丁的边缘和锥体外系效应中发挥作用。
Neuropeptides are linked to the psychopathology of stimulants of abuse, principally through dopamine mechanisms. Substance P (SP) is one of these neuropeptides and is associated with both limbic and extrapyramidal dopaminergic pathways and likely contributes to the pharmacology of these stimulants. The effects of nicotine on these dopamine systems have also been extensively studied; however, its effects on the associated SP pathways have received little attention.In the present study, we elucidated the effects of nicotine treatment on limbic and extrapyramidal SP systems by measuring changes in associated SP tissue concentrations.Male Sprague-Dawley rats received (+/-)nicotine 4.0 mg/kg/day (0.8 mg/kg, intraperitoneally; five injections at 2-h intervals) in the presence or absence of selective dopamine D-1 and D-2 receptor antagonists or a nonselective nicotinic acetylcholine receptor antagonist.The nicotine treatment significantly but temporarily decreased substance P-like immunoreactivity (SPLI) content in the ventral tegmental area (VTA) and substantia nigra 12-18 h after drug exposure. The nicotine-mediated changes in SPLI were selectively blocked by pretreatment with mecamylamine as well as a dopamine D-1, D-2, or both receptor antagonists. Other brain areas that also selectively demonstrated nicotine-related declines in SPLI content included prefrontal cortex, the nucleus accumbens shell, and the very posterior caudate.These findings indicate that some limbic and basal ganglia SP systems are significantly affected by exposure to nicotine through processes mediated by nicotinic and dopaminergic receptors, suggesting a role for SP pathways in nicotine's limbic and extrapyramidal effects.