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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors
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Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors

机译：茶碱（一种类似于咖啡因的嘌呤生物碱）对运动的激活：腺苷和多巴胺受体的参与

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摘要

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A 1 agonist, N 6-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A 2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino- 5′-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D 1 and D 2 receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D 1R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D 2R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.
机译：嘌呤化合物（例如咖啡因）具有许多促进健康的特性，并已证明对治疗许多不同的疾病有益。茶碱是一种结构上类似于咖啡因的嘌呤生物碱，大量存在于茶花茶中，最近已成为一种潜在的治疗化合物。在本研究中，使用啮齿动物行为模型对茶碱进行了测试，以研究该药物对运动活性的影响。向长Evans大鼠注射茶碱（24或48 mg / kg，腹腔注射），并测量其活动水平。结果显示，与对照动物相比，最高剂量的茶碱（48 mg / kg，i.p.）显着提高了运动能力，并且在整个疗程中活性一直保持升高。为了测试腺嘌呤的运动激活特性背后的腺苷受体的参与，向大鼠施用了腺苷A 1激动剂，N 6-环戊基腺苷（CPA; 0.1 mg / kg，ip）和A 2A受体激动剂2-p- （2-羧乙基）苯乙基氨基-5'-N-乙基羧酰胺基腺苷（CGS-21680; 0.2 mg / kg，ip）。用茶碱进行的预处理显着减轻了腺苷受体激动剂引起的运动抑制，表明茶碱可能起腺苷受体拮抗剂的作用。接下来，我们研究了DA D 1和D 2受体拮抗作用对茶碱引起的运动过度的作用。 D 1R SCH23390（0.1或0.05 mg / kg，ip）和D 2R依托必利（0.1 mg / kg，ip）两种拮抗剂均显着降低了茶碱刺激的活性，表明该行为反应至少部分是由DA介导的。受体。为了研究可引起茶碱作用的大脑区域，将该药物（10或20μg）从两侧注入伏隔核（NAc）。茶碱以剂量依赖性方式增强活性水平，暗示NAc在调节茶碱对运动的作用中的作用。此外，茶碱在长期暴露后不会引起运动性敏化或耐受性。综上所述，这些发现表明茶碱显着增强了活性。由腺苷能和多巴胺能系统介导的作用。

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