Gaynor C M, Handley S L
Pharmaceutical Sciences Research Institute, School of Life and Health Sciences, Aston University, Birmingham, UK.
Psychopharmacology (Berl). 2001 Jan;153(3):327-33. doi: 10.1007/s002130000558.
Nicotine appears to ameliorate the tics of Tourette syndrome. There is evidence that plasma concentrations of the tryptophan metabolite kynurenine may be elevated in this condition. Rodent head-shakes have been proposed as a putative model of Tourette syndrome and are potentiated by kynurenine.
To determine the effects of acute and chronic nicotine on mouse head-shakes, and to study whether nicotine influences brain and plasma levels of kynurenine and certain of its further metabolites in this species.
Behavioural and biochemical studies.
Acute (-10 min) administration of (-)-nicotine, or the nicotinic agonist (+)-epibatidine, dose dependently attenuated head-shakes induced by the 5-HT2A/2C receptor agonist +/-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). This attenuation was inhibited by the nicotinic receptor antagonist mecamylamine. Acute nicotine did not affect either spontaneous head-shakes or plasma and brain kynurenine. Fifteen hours after the last of twice daily injections of nicotine (1.6 mg/kg for 7 days), the frequency of spontaneous and DOI-induced head-shakes was significantly potentiated and there was a significant elevation of both plasma and brain kynurenine, although no differences were detected in plasma concentrations of tryptophan, kynurenic acid, 3-hydroxykynurenine or 3-hydroxyanthranilic acid. Brain levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid were also unaffected. In contrast, all these measures were unchanged 15 h after a single nicotine dose (1.6 mg/kg).
The acute studies indicate that head-shakes induced by DOI are indeed inhibited by nicotinic receptor agonists and suggest that this is not a consequence of an increase in kynurenine. While a role for kynurenine or its metabolites in increasing the head-shake rate after chronic nicotine cannot be excluded, alternative explanations included alterations in the expression or functional status of nicotinic receptor components and further work will be required to characterise this effect.
尼古丁似乎可改善抽动秽语综合征的抽动症状。有证据表明，在这种情况下色氨酸代谢产物犬尿氨酸的血浆浓度可能会升高。啮齿动物的头部抖动已被提议作为抽动秽语综合征的一种假定模型，并且会被犬尿氨酸增强。
确定急性和慢性尼古丁对小鼠头部抖动的影响，并研究尼古丁是否会影响该物种大脑和血浆中犬尿氨酸及其某些进一步代谢产物的水平。
行为学和生物化学研究。
急性（-10分钟）给予（-）-尼古丁或烟碱激动剂（+）-埃博霉素，剂量依赖性地减弱了5-HT2A/2C受体激动剂+/-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）诱导的头部抖动。这种减弱被烟碱受体拮抗剂美加明抑制。急性尼古丁对自发头部抖动或血浆及大脑中的犬尿氨酸均无影响。在每日两次注射尼古丁（1.6mg/kg，共7天）的最后一次注射后15小时，自发和DOI诱导的头部抖动频率显著增强，血浆和大脑中的犬尿氨酸均显著升高，尽管在色氨酸、犬尿酸、3-羟基犬尿氨酸或3-羟基邻氨基苯甲酸的血浆浓度中未检测到差异。大脑中5-羟色胺和5-羟吲哚乙酸的水平也未受影响。相比之下，单次给予尼古丁剂量（1.6mg/kg）15小时后，所有这些指标均未改变。
急性研究表明，DOI诱导的头部抖动确实受到烟碱受体激动剂的抑制，并表明这不是犬尿氨酸增加的结果。虽然不能排除犬尿氨酸或其代谢产物在慢性尼古丁后增加头部抖动频率中的作用，但其他解释包括烟碱受体成分的表达或功能状态的改变，需要进一步的研究来表征这种效应。
