過去進行斑馬魚實驗時，通常是藉由鑷子或幫浦等方式運輸麻醉後的幼魚。然而，透過這種方式可能會損傷幼魚且因幼魚處於麻醉狀態，無法有效的取得動態參數。本研究提出了一種創新的微流體平台，此平台結合了心跳、心血管系統以及胸鰭擺動的觀測成像，並結合光驅動技術，促使斑馬魚幼魚的視動行為 (Optomotor response) 產生，可將非麻醉的斑馬魚幼魚運輸至指定位置固定以進行高精度藥物測試。本研究選用乙醇以及咖啡因做為主要的藥物測試，這兩種物質皆為日常生活中攝取頻率極高的物質。根據研究報告指出，攝取過量的乙醇與咖啡因皆會對中樞神經及心血管系統造成影響，產生不規則的心跳頻率以及焦慮現象。本研究以斑馬魚做為藥物毒性測試的生物模型，並將胚胎暴露於乙醇溶液（3%）與咖啡因溶液（25 mg/L、65 mg/L）。研究數據顯示，暴露於乙醇與咖啡因皆會導致幼魚在各個成長階段 (5、7和9 d.p.f.) 的心跳頻率和平均血液流速降低，其中心跳的平均下降程度分別為15.4%、11.1%及8.7%；血液流速則下降了12.5%、6.3%及10.6%。實驗結果證實了心率與血液流速的相關性。為了進一步探討藥物的影響，量測了幼魚胸鰭擺動的能力，量化了胸鰭擺動所造成的時間平均環流量以及胸鰭擺動頻率。實驗結果觀察到，在發育早期 （5 d.p.f.），暴露於咖啡因溶液（25 mg/L）造成平均環流量有下降了35.1%，而在成長後期（7、9 d.p.f.）則上升了3.5%以及48.1%。而胸鰭擺動頻率的趨勢則與平均環流量不同，由於咖啡因的刺激，在各個成長階段皆呈現上升的趨勢，其中低濃度與高濃度之平均上升程度為12 %以及8.6 %。本研究中使用的微流體平台提供了良好的觀測條件，並透過實驗結果確認不同參數的變化。本研究確認了乙醇與咖啡因對斑馬魚幼魚的各項影響，且針對此影響與其他研究的比較，探討了心血管功能的變化與胸鰭擺動的量化所代表的藥物影響。此實驗方法的可行性與適用性已得到良好的驗證，未來對於斑馬魚測試能提供更全面的觀測平台，進而促進人類醫學與遺傳學的發展。

In the past, the experimental platform employing zebrafish (Danio rerio) research lacked a design that could avoid damage and freedom of imaging internal organs. To overcome the limitations of the traditional experimental method, this study proposed an innovative microfluidic device that combined the cardiovascular system and pectoral fin beating imaging and used the moving grating to transport the non-anesthetized zebrafish to the immobilized position, avoiding the opportunities of permanent injury to zebrafish larvae during the experiment also providing multiple imaging in the same device to facilitate drug screening. To further verify the potential of the proposed device for drug screening, this study used ethanol and caffeine as drug tests. Both drugs were drugs with a high daily intake, so animal models needed to be used to study their toxicity tests. The experiment results showed that exposure to both ethanol and caffeine would reduce the heartbeat and mean blood flow velocity of zebrafish at various growth stages (5, 7, and 9 d.p.f.). The average decrease in heartbeat were 15.4%, 11.1% and 8.7% respectively; 12.5%, 6.3% and 10.6% in mean blood flow velocity respectively. The experimental results confirmed the correlation between heartbeat and mean blood flow velocity. To further explored the effects of drugs, the circulation and beating frequency caused by pectoral fin were quantified. The experimental results observed that in the early stage of development (5 d.p.f.), exposure to caffeine (25 mg/L) the circulation decreased by 35.1%, while in the late stage of growth (7, 9 d.p.f.) it increased by 3.5% and 48.1% compared to the control group. The trend of the pectoral fin beat frequency was different from the circulation. Due to the stimulation of caffeine, it showed an upward trend in each growth stage. The average increased in low concentration and high concentration were 12% and 8.6%. The obtained findings can be applicable for future investigation in behavioral drug screening serving as the forefront in psychopharmacological and cognition research.

[1] B. B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, and E. E. Zvartau, "Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use," Pharmacological Reviews, vol. 51, no. 1, p. 83, 1999.
[2] F. E. Ahmed, "Toxicological effects of ethanol on human health," (in eng), Critical reviews in toxicology, vol. 25, no. 4, pp. 347-67, 1995.
[3] M. A. De Luca, V. Bassareo, A. Bauer, and G. Di Chiara, "Caffeine and accumbens shell dopamine," Journal of neurochemistry, vol. 103, no. 1, pp. 157-163, 2007.
[4] M. A. Beydoun et al., "Caffeine and alcohol intakes and overall nutrient adequacy are associated with longitudinal cognitive performance among US adults," The Journal of nutrition, vol. 144, no. 6, pp. 890-901, 2014.
[5] S. Ferré, "Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders," (in eng), Psychopharmacology, vol. 233, no. 10, pp. 1963-1979, 2016.
[6] C. Willson, "The clinical toxicology of caffeine: A review and case study," (in eng), Toxicol Rep, vol. 5, pp. 1140-1152, 2018.
[7] W. A. Hunt, "Ethanol and the Central Nervous System," in Medical and Social Aspects of Alcohol Abuse, B. Tabakoff, P. B. Sutker, and C. L. Randall, Eds. Boston, MA: Springer US, 1983, pp. 133-163.
[8] E. V. Sullivan, R. A. Harris, and A. Pfefferbaum, "Alcohol's effects on brain and behavior," Alcohol Research & Health, 2010.
[9] M. Wallner and R. W. Olsen, "Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development?," (in eng), Br J Pharmacol, vol. 154, no. 2, pp. 288-298, 2008.
[10] E. A. Budygin and J. L. Weiner, "Exploring the Neurochemical Basis of Alcohol Addiction-Related Behaviors: Translational Research," (in eng), Transl Biomed, vol. 6, no. Suppl Spec, 2015.
[11] S. Ferré, "Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders," (in eng), Psychopharmacology, vol. 233, no. 10, pp. 1963-79, May 2016.
[12] F. Weiss and L. J. Porrino, "Behavioral Neurobiology of Alcohol Addiction: Recent Advances and Challenges," The Journal of Neuroscience, vol. 22, no. 9, p. 3332, 2002.
[13] J. F. Greden, "Anxiety or caffeinism: a diagnostic dilemma," American Journal of Psychiatry, vol. 131, no. 10, pp. 1089-1092, 1974.
[14] J. A. Ewing, K. C. Mills, E. Z. Bisgrove, and K. McManus, "Selective Attenuation of Ethanol-Induced Performance Impairment by Nalozone in Humans," Advances in alcohol & substance abuse, vol. 3, no. 4, pp. 47-59, 1984.
[15] A. M. White, D. B. Matthews, and P. J. Best, "Ethanol, memory, and hippocampal function: a review of recent findings," Hippocampus, vol. 10, no. 1, pp. 88-93, 2000.
[16] I. Rusyn and R. Bataller, "Alcohol and toxicity," (in eng), J Hepatol, vol. 59, no. 2, pp. 387-388, 2013.
[17] J. R. Meyers, "Zebrafish: Development of a Vertebrate Model Organism," Current Protocols Essential Laboratory Techniques, vol. 16, no. 1, p. e19, 2018.
[18] K. Howe et al., "The zebrafish reference genome sequence and its relationship to the human genome," Nature, vol. 496, no. 7446, pp. 498-503, 2013/04/01 2013.
[19] S. Guo, "Using zebrafish to assess the impact of drugs on neural development and function," Expert Opinion on Drug Discovery, vol. 4, no. 7, pp. 715-726, 2009/07/01 2009.
[20] D. R. Brown, L. A. Samsa, L. Qian, and J. Liu, "Advances in the Study of Heart Development and Disease Using Zebrafish," Journal of Cardiovascular Development and Disease, vol. 3, no. 2, 2016.
[21] A. M. Stewart, O. Braubach, J. Spitsbergen, R. Gerlai, and A. V. Kalueff, "Zebrafish models for translational neuroscience research: from tank to bedside," Trends in Neurosciences, vol. 37, no. 5, pp. 264-278, 2014/05/01/ 2014.
[22] P. McGrath and C.-Q. Li, "Zebrafish: a predictive model for assessing drug-induced toxicity," Drug Discovery Today, vol. 13, no. 9, pp. 394-401, 2008/05/01/ 2008.
[23] P. V. Asharani, Y. Lian Wu, Z. Gong, and S. Valiyaveettil, "Toxicity of silver nanoparticles in zebrafish models," Nanotechnology, vol. 19, no. 25, p. 255102, 2008/05/14 2008.
[24] P. K. Chan, C. C. Lin, and S. H. Cheng, "Noninvasive technique for measurement of heartbeat regularity in zebrafish (Danio rerio) embryos," BMC Biotechnology, vol. 9, no. 1, p. 11, 2009/02/19 2009.
[25] C. Xu, S. Volkery, and A. F. Siekmann, "Intubation-based anesthesia for long-term time-lapse imaging of adult zebrafish," Nature Protocols, vol. 10, no. 12, pp. 2064-2073, 2015/12/01 2015.
[26] F. Yang, C. Gao, P. Wang, G.-J. Zhang, and Z. Chen, "Fish-on-a-chip: microfluidics for zebrafish research," Lab on a Chip, 10.1039/C6LC00044D vol. 16, no. 7, pp. 1106-1125, 2016.
[27] K. Mani, T.-C. Chang Chien, B. Panigrahi, and C.-Y. Chen, "Manipulation of zebrafish’s orientation using artificial cilia in a microchannel with actively adaptive wall design," Scientific Reports, vol. 6, no. 1, p. 36385, 2016/11/08 2016.
[28] T. Y. Chang, C. Pardo-Martin, A. Allalou, C. Wählby, and M. F. Yanik, "Fully automated cellular-resolution vertebrate screening platform with parallel animal processing," (in eng), Lab Chip, vol. 12, no. 4, pp. 711-6, Feb 21 2012.
[29] F. Pinto-Teixeira, M. Muzzopappa, J. Swoger, A. Mineo, J. Sharpe, and H. López-Schier, "Intravital imaging of hair-cell development and regeneration in the zebrafish," (in eng), Front Neuroanat, vol. 7, pp. 33-33, 2013.
[30] R. Willemsen, S. v. t. Padje, J. C. van Swieten, and B. A. Oostra, "Zebrafish (Danio rerio) as a Model Organism for Dementia," in Animal Models of Dementia, P. P. De Deyn and D. Van Dam, Eds. Totowa, NJ: Humana Press, 2011, pp. 255-269.
[31] M. Watchon et al., "Calpain Inhibition Is Protective in Machado–Joseph Disease Zebrafish Due to Induction of Autophagy," The Journal of Neuroscience, vol. 37, no. 32, p. 7782, 2017.
[32] T. Brand, "Heart development: molecular insights into cardiac specification and early morphogenesis," Developmental Biology, vol. 258, no. 1, pp. 1-19, 2003/06/01/ 2003.
[33] J. Bakkers, "Zebrafish as a model to study cardiac development and human cardiac disease," (in eng), Cardiovasc Res, vol. 91, no. 2, pp. 279-288, 2011.
[34] A. Au - Evangelisti et al., "High-Frequency Ultrasound Echocardiography to Assess Zebrafish Cardiac Function," JoVE, no. 157, p. e60976, 2020/03/12/ 2020.
[35] D. Bournele and D. Beis, "Zebrafish models of cardiovascular disease," Heart Failure Reviews, vol. 21, no. 6, pp. 803-813, 2016/11/01 2016.
[36] R. J. Major and K. D. Poss, "Zebrafish Heart Regeneration as a Model for Cardiac Tissue Repair," (in eng), Drug Discov Today Dis Models, vol. 4, no. 4, pp. 219-225, 2007.
[37] C. van Opbergen, S. Voorn, M. Vos, T. de Boer, and T. van Veen, "Cardiac Ca 2+ signalling in zebrafish: Translation of findings to man," Progress in Biophysics and Molecular Biology, vol. 138, 05/01 2018.
[38] B. London, "Cardiac Arrhythmias: From (Transgenic) Mice to Men," Journal of Cardiovascular Electrophysiology, vol. 12, no. 9, pp. 1089-1091, 2001.
[39] W. Risau, "Differentiation of endothelium," The FASEB journal, vol. 9, no. 10, pp. 926-933, 1995.
[40] E. Ellertsdóttir et al., "Vascular morphogenesis in the zebrafish embryo," Developmental Biology, vol. 341, no. 1, pp. 56-65, 2010/05/01/ 2010.
[41] S. Isogai, M. Horiguchi, and B. M. Weinstein, "The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development," (in eng), Dev Biol, vol. 230, no. 2, pp. 278-301, Feb 15 2001.
[42] H. Grandel and S. Schulte-Merker, "The development of the paired fins in the Zebrafish (Danio rerio)," Mechanisms of Development, vol. 79, no. 1, pp. 99-120, 1998/12/01/ 1998.
[43] D. H. Thorsen, J. J. Cassidy, and M. E. Hale, "Swimming of larval zebrafish: fin-axis coordination and implications for function and neural control," (in eng), J Exp Biol, vol. 207, no. Pt 24, pp. 4175-83, Nov 2004.
[44] J. W. M. Osse and J. G. M. van den Boogaart, "Dynamic morphology of fish larvae, structural implications of friction forces in swimming, feeding and ventilation*," Journal of Fish Biology, https://doi.org/10.1111/j.1095-8649.1999.tb01053.x vol. 55, no. sA, pp. 156-174, 1999/12/01 1999.
[45] M. H. Green, R. K. Ho, and M. E. Hale, "Movement and function of the pectoral fins of the larval zebrafish (Danio rerio) during slow swimming," (in eng), J Exp Biol, vol. 214, no. Pt 18, pp. 3111-23, Sep 15 2011.
[46] M. H. Green, O. M. Curet, N. A. Patankar, and M. E. Hale, "Fluid dynamics of the larval zebrafish pectoral fin and the role of fin bending in fluid transport," (in eng), Bioinspiration & biomimetics, vol. 8, no. 1, p. 016002, Mar 2013.
[47] A. M. Zimmer, M. Mandic, K. M. Rourke, and S. F. Perry, "Breathing with fins: do the pectoral fins of larval fishes play a respiratory role?," (in eng), American journal of physiology. Regulatory, integrative and comparative physiology, vol. 318, no. 1, pp. R89-r97, Jan 1 2020.
[48] C. Parng, W. L. Seng, C. Semino, and P. McGrath, "Zebrafish: a preclinical model for drug screening," (in eng), Assay and drug development technologies, vol. 1, no. 1 Pt 1, pp. 41-8, Nov 2002.
[49] L. N. Huiting, F. Laroche, and H. Feng, "The Zebrafish as a Tool to Cancer Drug Discovery," (in eng), Austin J Pharmacol Ther, vol. 3, no. 2, pp. 1069-1069, 2015.
[50] I. Miyawaki, "Application of zebrafish to safety evaluation in drug discovery," (in eng), J Toxicol Pathol, vol. 33, no. 4, pp. 197-210, 2020.
[51] C. A. MacRae and R. T. Peterson, "Zebrafish as tools for drug discovery," Nature Reviews Drug Discovery, vol. 14, no. 10, pp. 721-731, 2015/10/01 2015.
[52] L. L. Bischel, B. R. Mader, J. M. Green, A. Huttenlocher, and D. J. Beebe, "Zebrafish Entrapment By Restriction Array (ZEBRA) device: a low-cost, agarose-free zebrafish mounting technique for automated imaging," Lab on a Chip, vol. 13, no. 9, pp. 1732-1736, 2013.
[53] N. M. Fuad, J. Kaslin, and D. Wlodkowic, "Lab-on-a-Chip imaging micro-echocardiography (iμEC) for rapid assessment of cardiovascular activity in zebrafish larvae," Sensors and Actuators B: Chemical, vol. 256, pp. 1131-1141, 2018.
[54] J. Bak-Coleman, D. Smith, and S. Coombs, "Going with, then against the flow: evidence against the optomotor hypothesis of fish rheotaxis," Animal Behaviour, vol. 107, pp. 7-17, 2015.
[55] S. S. Easter Jr and G. N. Nicola, "The development of eye movements in the zebrafish (Danio rerio)," Developmental Psychobiology: The Journal of the International Society for Developmental Psychobiology, vol. 31, no. 4, pp. 267-276, 1997.
[56] O. Rinner, J. M. Rick, and S. C. F. Neuhauss, "Contrast Sensitivity, Spatial and Temporal Tuning of the Larval Zebrafish Optokinetic Response," Investigative Ophthalmology & Visual Science, vol. 46, no. 1, pp. 137-142, 2005.
[57] S. C. Neuhauss et al., "Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish," Journal of Neuroscience, vol. 19, no. 19, pp. 8603-8615, 1999.
[58] D. T. Clark, "VISUAL RESPONSES IN DEVELOPING ZEBRAFISH (BRACHYDANIO RERIO)," 1982.
[59] R. Portugues and F. Engert, "The neural basis of visual behaviors in the larval zebrafish," Current Opinion in Neurobiology, vol. 19, no. 6, pp. 644-647, 2009/12/01/ 2009.
[60] M. B. Orger, M. C. Smear, S. M. Anstis, and H. Baier, "Perception of Fourier and non-Fourier motion by larval zebrafish," Nature Neuroscience, vol. 3, no. 11, pp. 1128-1133, 2000/11/01 2000.
[61] M. K. LeFauve, C. J. Rowe, M. Crowley-Perry, J. L. Wiegand, A. G. Shapiro, and V. P. Connaughton, "Using a variant of the optomotor response as a visual defect detection assay in zebrafish," (in eng), J Biol Methods, vol. 8, no. 1, p. e144, 2021.
[62] K. Mani, Y.-C. Hsieh, B. Panigrahi, and C.-Y. Chen, "A noninvasive light driven technique integrated microfluidics for zebrafish larvae transportation," Biomicrofluidics, vol. 12, no. 2, p. 021101, 2018.
[63] L. M. Hines and E. B. Rimm, "Moderate alcohol consumption and coronary heart disease: a review," Postgraduate Medical Journal, vol. 77, no. 914, p. 747, 2001.
[64] T. S. Naimi, R. D. Brewer, A. Mokdad, C. Denny, M. K. Serdula, and J. S. Marks, "Binge drinking among US adults," (in eng), Jama, vol. 289, no. 1, pp. 70-5, Jan 1 2003.
[65] A. S. Brecher, "93 - The Effect of Acetaldehyde on Plasma  The author is grateful to the Northwest Ohio Chapter, Inc. of the American Heart Association for supporting much of the research. Additional support from Michael H. Basista, M.D., Medical College of Ohio at Toledo and from Mr Robert Harr of the Medical Technology program at Bowling Green State University is gratefully acknowledged," in Comprehensive Handbook of Alcohol Related Pathology, V. R. Preedy and R. R. Watson, Eds. Oxford: Academic Press, 2005, pp. 1223-1244.
[66] V. Santhakumar, M. Wallner, and T. S. Otis, "Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition," (in eng), Alcohol (Fayetteville, N.Y.), vol. 41, no. 3, pp. 211-221, 2007.
[67] A. Nehlig, J.-L. Daval, and G. Debry, "Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects," Brain Research Reviews, vol. 17, no. 2, pp. 139-170, 1992/05/01/ 1992.
[68] A. Kugelman and M. Durand, "A comprehensive approach to the prevention of bronchopulmonary dysplasia," Pediatric Pulmonology, vol. 46, no. 12, pp. 1153-1165, 2011.
[69] A. Cano-Marquina, J. J. Tarín, and A. Cano, "The impact of coffee on health," Maturitas, vol. 75, no. 1, pp. 7-21, 2013/05/01/ 2013.
[70] M. E. Angelucci, C. Cesário, R. H. Hiroi, P. L. Rosalen, and C. Da Cunha, "Effects of caffeine on learning and memory in rats tested in the Morris water maze," (in eng), Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, vol. 35, no. 10, pp. 1201-8, Oct 2002.
[71] M. A. Tarnopolsky, "Caffeine and Creatine Use in Sport," Annals of Nutrition and Metabolism, vol. 57(suppl 2), no. Suppl. 2, pp. 1-8, 2010.
[72] A. J. Budney and J. A. Emond, "Caffeine addiction? Caffeine for youth? Time to act!," Addiction, vol. 109, no. 11, pp. 1771-1772, 2014.
[73] J. J. Barone and H. R. Roberts, "Caffeine consumption," Food and Chemical Toxicology, vol. 34, no. 1, pp. 119-129, 1996/01/01/ 1996.
[74] L. López-Cruz et al., "Ethanol and Caffeine Effects on Social Interaction and Recognition in Mice: Involvement of Adenosine A(2A) and A(1) Receptors," (in eng), Front Behav Neurosci, vol. 10, pp. 206-206, 2016.
[75] J. Woodward, "Principles of Addiction Medicine," 2009.
[76] S. Ferré and M. C. O'Brien, "Alcohol and Caffeine: The Perfect Storm," (in eng), J Caffeine Res, vol. 1, no. 3, pp. 153-162, 2011.
[77] R. E. Hernandez, L. Galitan, J. Cameron, N. Goodwin, and L. Ramakrishnan, "Delay of Initial Feeding of Zebrafish Larvae Until 8 Days Postfertilization Has No Impact on Survival or Growth Through the Juvenile Stage," (in eng), Zebrafish, vol. 15, no. 5, pp. 515-518, Oct 2018.
[78] S. Subendran, Y.-C. Wang, Y.-H. Lu, and C.-Y. Chen, "The evaluation of zebrafish cardiovascular and behavioral functions through microfluidics," Scientific Reports, vol. 11, no. 1, p. 13801, 2021/07/05 2021.
[79] J. Kompenhans et al., Particle Image Velocimetry in Aerodynamics: Technology and Applications in Wind Tunnels. 1999.
[80] Y. Sugii, K. Okamoto, A. Hibara, M. Tokeshi, and T. Kitamori, "Stabilization of interface between two liquid phases on a microchip by means of micro PIV technique," 01/01 2003.
[81] P. Rombough, "Gills are needed for ionoregulation before they are needed for O2 uptake in developing zebrafish, Danio rerio," Journal of Experimental Biology, vol. 205, no. 12, pp. 1787-1794, 2002.
[82] T. Schwerte, C. Prem, A. Mairösl, and B. Pelster, "Development of the sympatho-vagal balance in the cardiovascular system in zebrafish (Danio rerio) characterized by power spectrum and classical signal analysis," (in eng), J Exp Biol, vol. 209, no. Pt 6, pp. 1093-100, Mar 2006.
[83] T. Schwerte, S. Voigt, and B. Pelster, "Epigenetic variations in early cardiovascular performance and hematopoiesis can be explained by maternal and clutch effects in developing zebrafish (Danio rerio)," (in eng), Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, vol. 141, no. 2, pp. 200-9, Jun 2005.
[84] F. Santoso et al., "Development of a Simple ImageJ-Based Method for Dynamic Blood Flow Tracking in Zebrafish Embryos and Its Application in Drug Toxicity Evaluation," Inventions, vol. 4, no. 4, 2019.
[85] J. Bilotta, J. A. Barnett, L. Hancock, and S. Saszik, "Ethanol exposure alters zebrafish development: a novel model of fetal alcohol syndrome," (in eng), Neurotoxicol Teratol, vol. 26, no. 6, pp. 737-43, Nov-Dec 2004.
[86] V. Vengeliene, A. Bilbao, A. Molander, and R. Spanagel, "Neuropharmacology of alcohol addiction," (in eng), Br J Pharmacol, vol. 154, no. 2, pp. 299-315, May 2008.
[87] R. T. Martin and T. Bartman, "Analysis of heart valve development in larval zebrafish," Developmental Dynamics, vol. 238, no. 7, pp. 1796-1802, 2009.
[88] N. Rana et al., "Caffeine-Induced Effects on Heart Rate in Zebrafish Embryos and Possible Mechanisms of Action: An Effective System for Experiments in Chemical Biology," Zebrafish, vol. 7, no. 1, pp. 69-81, 2010/03/01 2010.
[89] C. R. Rush, S. T. Higgins, J. R. Hughes, W. K. Bickel, and M. S. Wiegner, "Acute behavioral and cardiac effects of alcohol and caffeine, alone and in combination, in humans," (in eng), Behavioural pharmacology, vol. 4, no. 6, pp. 562-572, Dec 1989.
[90] D. J. Milan and C. A. MacRae, "Zebrafish genetic models for arrhythmia," Progress in biophysics and molecular biology, vol. 98, no. 2-3, pp. 301-308, 2008.
[91] B. Vogel et al., "In-vivo characterization of human dilated cardiomyopathy genes in zebrafish," Biochemical and biophysical research communications, vol. 390, no. 3, pp. 516-522, 2009.
[92] F. M. Benslimane et al., "Cardiac function and blood flow hemodynamics assessment of zebrafish (Danio rerio) using high-speed video microscopy," Micron, vol. 136, p. 102876, 2020/09/01/ 2020.
[93] B. Lockwood, S. Bjerke, K. Kobayashi, and S. Guo, "Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening," Pharmacology Biochemistry and Behavior, vol. 77, no. 3, pp. 647-654, 2004/03/01/ 2004.
[94] R. C. MacPhail, J. Brooks, D. L. Hunter, B. Padnos, T. Irons, and S. Padilla, "Locomotion in larval zebrafish: Influence of time of day, lighting and ethanol," Neurotoxicology, vol. 30, pp. 52-8, 11/01 2008.
[95] R. Gerlai, M. Lahav, S. Guo, and A. Rosenthal, "Drinks like a fish: zebra fish (Danio rerio) as a behavior genetic model to study alcohol effects," (in eng), Pharmacology, biochemistry, and behavior, vol. 67, no. 4, pp. 773-82, Dec 2000.
[96] N. Guo et al., "Influences of acute ethanol exposure on locomotor activities of zebrafish larvae under different illumination," Alcohol, vol. 49, no. 7, pp. 727-737, 2015.
[97] L. C. Santos, J. Ruiz-Oliveira, P. F. Silva, and A. C. Luchiari, "Caffeine dose–response relationship and behavioral screening in zebrafish," The question of caffeine, pp. 87-105, 2017.
[98] C. Maximino, M. G. Lima, K. R. M. Olivera, D. L. W. Picanço-Diniz, and A. M. Herculano, "Adenosine A1, but not A2, Receptor Blockade Increases Anxiety and Arousal in Zebrafish," Basic & Clinical Pharmacology & Toxicology, vol. 109, no. 3, pp. 203-207, 2011.
[99] M. E. Yacoubi, C. Ledent, J. F. Ménard, M. Parmentier, J. Costentin, and J. M. Vaugeois, "The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A2A receptors," Br J Pharmacol, vol. 129, no. 7, pp. 1465-1473, 2000.
[100] K. M. Capiotti et al., "Early exposure to caffeine affects gene expression of adenosine receptors, DARPP-32 and BDNF without affecting sensibility and morphology of developing zebrafish (Danio rerio)," Neurotoxicology and Teratology, vol. 33, no. 6, pp. 680-685, 2011/11/01/ 2011.
[101] C. L. Drake, T. Roehrs, L. Turner, H. M. Scofield, and T. Roth, "Caffeine Reversal of Ethanol Effects on the Multiple Sleep Latency Test, Memory, and Psychomotor Performance," Neuropsychopharmacology, vol. 28, no. 2, pp. 371-378, 2003/02/01 2003.
[102] B. M. Fritz, M. Companion, and S. L. Boehm, "“Wired,” Yet Intoxicated: Modeling Binge Caffeine and Alcohol Co-Consumption in the Mouse," Alcoholism: Clinical and Experimental Research, https://doi.org/10.1111/acer.12472 vol. 38, no. 8, pp. 2269-2278, 2014/08/01 2014.
[103] A. V. Kalueff et al., "Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond," (in eng), Zebrafish, vol. 10, no. 1, pp. 70-86, Mar 2013.