Shi D, Nikodijević O, Jacobson K A, Daly J W
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Arch Int Pharmacodyn Ther. 1994 Nov-Dec;328(3):261-87.
Chronic ingestion of caffeine by male NIH Swiss strain mice leads in about 3 days to a significant increase in A1-adenosine, nicotinic and muscarinic receptors, and a significant decrease of beta 1-adrenoceptors in cerebral cortical membranes. Plasma levels of caffeine in the chronically treated mice range from 0.70 to 5.7 micrograms/ml. The changes in receptors reverse after withdrawal of caffeine within 7 days. An increase in nitrendipine binding sites, associated with L-type calcium channels, also occurs within 4 days and has reversed in 7 days after withdrawal. There is no change in the levels of striatal nicotinic receptors of D2-dopamine receptors, nor of [3H]cocaine binding to dopamine uptake sites. Levels of opioid receptors are either increased (delta) or unaltered (mu, kappa). sigma-Receptors are unaltered. Stimulations of striatal adenylate cyclase by forskolin, dopamine and NECA are not significantly affected after chronic caffeine ingestion. The adenosine agonist, NECA, reverses the amphetamine-elicited increases in locomotor activity and partly reverses the cocaine-elicited increases. The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice. NECA reverses the stimulation of locomotor activity elicited by the muscarinic antagonist, scopolamine, and is more effective in the chronic caffeine mice. The behavioral depressant effects of the muscarinic agonist, oxotremorine, are not markedly altered after chronic caffeine ingestion.
雄性NIH瑞士品系小鼠长期摄入咖啡因约3天后，大脑皮质膜中的A1 - 腺苷、烟碱和毒蕈碱受体显著增加，β1 - 肾上腺素能受体显著减少。长期接受咖啡因治疗的小鼠血浆咖啡因水平在0.70至5.7微克/毫升之间。在停用咖啡因7天内，受体变化会逆转。与L型钙通道相关的尼群地平结合位点在4天内也会增加，并在停药7天后逆转。纹状体烟碱受体、D2 - 多巴胺受体水平以及[3H]可卡因与多巴胺摄取位点的结合均无变化。阿片受体水平要么增加（δ型），要么未改变（μ型、κ型）。σ受体未改变。长期摄入咖啡因后，福斯高林、多巴胺和NECA对纹状体腺苷酸环化酶的刺激作用无显著影响。腺苷激动剂NECA可逆转苯丙胺引起的运动活动增加，并部分逆转可卡因引起的运动活动增加。在对照小鼠中，NECA剂量 - 反应曲线对苯丙胺呈多相性（抑制、刺激然后抑制），但在长期摄入咖啡因的小鼠中对苯丙胺仅呈抑制作用，而在对照小鼠和长期摄入咖啡因的小鼠中对可卡因均呈多相性。NECA可逆转毒蕈碱拮抗剂东莨菪碱引起的运动活动刺激，且在长期摄入咖啡因的小鼠中更有效。长期摄入咖啡因后，毒蕈碱激动剂氧化震颤素的行为抑制作用无明显改变。
