Phenylalanine Rich Diet (Vicia faba L.) Enhances the Expression of Dopamine Receptor D3 (DRD3) Gene in Rabbits


  •   Ghada Mostafa Shebl

  •   Hanan Ibrahim Sayed-Ahmed

  •   Mohamed Bassuony Hamza

  •   Ashraf Salah El-Din Haider


Dopamine is a neurotransmitter hormone for pleasure and reward. It is synthesized only in the brain cells of human and animals and responsible for the regulation of behavior, mood, memory, cognitive, flexible movement, the body weight, and other important functions. The Dopamine Receptor D3 (DRD3) is the most important receptor for dopamine. In this investigation, expression of DRD3 gene was studied in rabbits fed on supplemented diet of dry and fresh faba bean (Vicia faba L. Sakha 3). DRD3 gene (≈ 1200 bp) in control and treated rabbits were PCR amplified, sequenced and aligned with reference gene (Acc. No XM_017346708.1). High genetic similarity values were detected among all sequences. DRD3 gene sequences of control, fresh and dry faba bean fed rabbits were deposited in the GenBank with accession numbers MZ714134, MZ714135 and MZ714136 respectively. Direct estimation of blood phenylalanine (Phe) amino acid indicated that feeding rabbits on dry faba bean reflected the highest level of Phe in the rabbit’s blood. Quantitative RT-qPCR analysis showed that DRD3 gene was over expressed after feeding rabbits on dry faba bean form compared with feeding on green form and control. Thus, diet rich with phenylalanine like Sakha3 (dry and fresh forms) enhance gene expression of DRD3 gene. However, diet doesn't affect the DRD3 gene sequence and structure. In a conclusion, our findings indicated a direct effect of faba bean supplemented diet on increasing DRD3 expression levels which improve the life quality for human.

Keywords: Dopamine Receptor D3 (DRD3), faba bean, Oryctolagus cuniculus, RT-qPCR


D. Martins, M. A. Mehta and D. Prata, "The “highs and lows” of the human brain on dopaminergics: Evidence from neuropharmacology," Neuroscience and Biobehavioral Reviews 80, 351-371, 2017.

E. Galaj, A. H. Newman and Z. X. Xi, "Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges," Neuroscience & Biobehavioral Reviews 114, 38-52, 2020.

X. Dong, Z. Liao, D. Gritsch, Y. Hadzhiev, Y. Bai, J. J. Locascio and C. H. Adler, "Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease," Nature Neuroscience 21(10): 1482-1492, 2018.

D. Benton and H. A. Young, "A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?" International Journal of Obesity, 40(1): S12-S21, 2016.

G. J. J. M. D. T. Ayano, "Dopamine: receptors, functions, synthesis, pathways, locations and mental disorders: review of literatures," Journal of Mental Disorders and Treatments 2(120): 2, 2016.

C. Borwick, R. Lal, L. W. Lim, C. J. Stagg and L. Aquili, "Dopamine depletion effects on cognitive flexibility as modulated by tDCS of the dlPFC," Brain Stimulation 13(1): 105-108, 2020.

K. Sreedevi, "Dopamine Dynamics in Dermatology and Behavioural Science," Journal of Addiction Science 6(2): 34-36, 2020.

X. Pan, A. C. Kaminga, S. Wen, X. Wu, K. Acheampong and A. Liu, "Dopamine and dopamine receptors in Alzheimer’s disease: A systematic review and network meta-analysis," Frontiers in Aging Neuroscience 11, 175, 2019.

P. Yang, W. C. Knight, H. Li, Y. Guo, J. S. Perlmutter, T. L. Benzinger and J. Xu, "Dopamine D1+ D3 receptor density may correlate with Parkinson disease clinical features," Annals of Clinical and Translational Neurology 8(1): 224-237, 2021.

L. F. Burbulla, and D. Krainc, "The role of dopamine in the pathogenesis of GBA1 linked Parkinson's disease," Neurobiology of Disease 132, 104545, 2019.

M. J. Armstrong and M.S. Okun, "Diagnosis and treatment of Parkinson disease: a review," Jama 323(6): 548-560, 2020.

D. Matuskey, G. A. Angarita, P. Worhunsky, S. Koohsari, P. Gravel, B. Pittman and R. T. Malison, "Dopamine D2/3 receptor availability in cocaine use disorder individuals with obesity as measured by [11C] PHNO PET," Drug and Alcohol Dependence 220, 108514, 2021.

R. A. Wise and M. A. Robble, "Dopamine and addiction," Annual Review of Psychology 71, 79-106, 2020.

A. Sanna, L. Fattore, P. Badas, G. Corona and M. Diana, "The hypodopaminergic state ten years after: transcranial magnetic stimulation as a tool to test the dopamine hypothesis of drug addiction,” Current Opinion in Pharmacology 56, 61-67, 2021.

E. Reimann, K. Kingo, M. Karelson, P. Reemann, U. Loite, M. Keermann and S. Kõks, "Expression profile of genes associated with the dopamine pathway in vitiligo skin biopsies and blood sera," Dermatology 224(2): 168-176,2012.

M. S. Al Abadie and D. J. Gawkrodger, "Integrating neuronal involvement into the immune and genetic paradigm of vitiligo," Clinical and Experimental Dermatology 46(4): 646-650, 2021.

G. Shebl, H. Sayed Ahmed, A. Kato, H. Dawoud, M. Hamza and A. Haider, "Detection of sequence mutations in phenylalanine hydroxylase (PAH) gene isolated from Egyptian Phenylketonuria (PKU) patients," Egyptian Journal of Expertimental Biology (Botany) 15(2): 295-301, 2019.

A. MacDonald, A. M. J. van Wegberg, K. Ahring, S. Beblo, A. Bélanger-Quintana, A. Burlina and S. C. Huijbregts, "PKU dietary handbook to accompany PKU guidelines," Orphanet Journal of Rare Diseases 15(1): 1-21, 2020.

H. R. Shoraka, A. A. Haghdoost, M. R. Baneshi, Z. Bagherinezhad and F. Zolala, "Global prevalence of classic phenylketonuria based on Neonatal Screening Program Data: systematic review and meta-analysis," Clinical and Experimental Pediatrics 63(2): 34, 2020.

A. Lopez, B. Havranek, G. A. Papadantonakis and S. M. Islam, "In silico screening and molecular dynamics simulation of deleterious PAH mutations responsible for phenylketonuria genetic disorder," Proteins: Structure, Function, and Bioinformatics 89(6): 683-696, 2021.

K. P. Siju, J. F. De Backer and I. C. G. Kadow, "Dopamine modulation of sensory processing and adaptive behavior in flies," Cell and Tissue Research 1-19, 2021.

M. Romanov, N. V. Dementieva, E. S. Fedorova, A. A. Krutikova, O. V. Mitrofanova, O. İ. Stanishevskaya and V. P. Terletsky, "Genetic variability of indels in the prolactin and dopamine receptor D2 genes and their association with the yield of allanto-amniotic fluid in Russian White laying hens," Journal of Agricultural Sciences 26(3): 373-379,2020.

J. Britto‐Júnior, N. J. Antunes, R. Campos, M. Sucupira, G. D. Mendes, F. Fernandes and G. De Nucci, "Determination of dopamine, noradrenaline, and adrenaline in Krebs-Henseleit solution by liquid chromatography coupled with tandem mass spectrometry and measurement of their basal release from Chelonoidis carbonaria aortae in vitro," Biomedical Chromatography 35(2): e4978, 2021.

C. A. Marsden, "Dopamine: the rewarding years," British Journal of Pharmacology 147(S1): S136-S144, 2006.

S. Yoon, S.C. Ji, J. Yang, Y. K. Kim, S. Lee, K. S. Yu and J. Y. Cho, "Ursodeoxycholic acid improves liver function via phenylalanine/tyrosine pathway and microbiome remodelling in patients with liver dysfunction,"Scientific Reports 8(1): 1-11, 2018.

M. Jaber, S. W. Robinson, C. Missale and M. G. Caron, "Dopamine receptors and brain function," Neuropharmacology 35(11): 1503-1519,1996.

J. M. Beaulieu and R. R. Gainetdinov, "The physiology, signaling, and pharmacology of dopamine receptors," Pharmacological Reviews 63(1): 182-217, 2011.

A. B. Ruzilawati, M. A. Islam, S. K. S. Muhamed and I. Ahmad, "Smoking Genes: A Case–Control Study of Dopamine Transporter Gene (SLC6A3) and Dopamine Receptor Genes (DRD1, DRD2 and DRD3) Polymorphisms and Smoking Behaviour in a Malay Male Cohort," Biomolecules 10(12): 1633, 2020.

J. Diaz, C. Pilon, B. Le Foll, C. Gros, A. Triller, J. C. Schwartz and P. Sokoloff, "Dopamine D3 receptors expressed by all mesencephalic dopamine neurons," Journal of Neuroscience 20(23): 8677-8684, 2000.

T. Ott and A. Nieder, "Dopamine D2 receptors enhance population dynamics in primate prefrontal working memory circuits," Cerebral Cortex 27(9): 4423-4435, 2017.

Z. B. You, J. T. Gao, G. H. Bi, Y. He, C. Boateng, J. Cao and Z. X. Xi, "The novel dopamine D3 receptor antagonists/partial agonists CAB2-015 and BAK4-54 inhibit oxycodone-taking and oxycodone-seeking behavior in rats," Neuropharmacology 126, 190-199, 2017.

J. P. Prieto, B. González, J. Muñiz, V. Bisagno and C. Scorza, "Molecular changes in the nucleus accumbens and prefrontal cortex associated with the locomotor sensitization induced by coca paste seized samples," Psychopharmacology 1-11, 2020.

A. G. Stanfill and X. Cao,"Expression of Dopamine-Related Genes in Four Human Brain Regions," Brain Sciences 10(8): 567, 2020.

R. Guerrero-Bautista, A. Franco-García, J. M. Hidalgo, F. J. Fernández-Gómez, B. Ribeiro Do Couto, M. Milanés and C. Núñez, "Distinct regulation of dopamine D3 receptor in the basolateral amygdala and dentate gyrus during the reinstatement of cocaine CPP induced by drug priming and social stress," International Journal of Molecular Sciences 22(6): 3100, 2021.

S. A. Bravo, C. Rangel-Barajas and B. F. Garduño, "Pathophysiology of L-Dopa Induced Dyskinesia—Changes in D1/D3 Receptors and Their Signaling Pathway," A Synopsis of Parkinson's Disease 119, 2014.

P. Yang, W. C. Knight, H. Li, Y. Guo, J. S. Perlmutter, T. L. Benzinger and J. Xu, "Dopamine D1+ D3 receptor density may correlate with Parkinson disease clinical features," Annals of Clinical and Translational Neurology 8(1): 224-237, 2021.

N. M. Appel, S. H. Li, T. H. Holmes, and J. B. Acri, "Dopamine D3 receptor antagonist (GSK598809) potentiates the hypertensive effects of cocaine in conscious, freely-moving dogs," Journal of Pharmacology and Experimental Therapeutics 354(3): 484-492, 2015.

P. Sokoloff and B. Le Foll, "The dopamine D3 receptor, a quarter century later,"European Journal of Neuroscience 45(1): 2-19, 2017.

Z. X. Xi and E. L. Gardner, "Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction,"CNS Drug Reviews 13(2): 240-259, 2007.

F. Müller-Schöttle, A. Bogusz, J. Grötzinger, A. Herrler, C. A. Krusche, K. Beier-Hellwig and H. M. Beier, "Full-length complementary DNA and the derived amino acid sequence of horse uteroglobin," Biology of Reproduction 66(6): 1723-1728, 2002.

M. H. Hendawey and A. M. A. Younes, "Biochemical evaluation of some faba bean cultivars under rainfed conditions at El-Sheikh Zuwayid," Annals of Agricultural Sciences 58(2): 183-193, 2013.

G. Shebl, H. Sayed Ahmed, A. Kato and A. Haider, "ISSR markers of some faba bean (Vicia faba L.) genotypes in relation to phenylalanine accumulation," Egyptian Journal of. Expertimental Biology (Botany) 14(1): 73-82, 2018. ‏

P. J. Esteves, J. Abrantes, H. M. Baldauf, L. BenMohamed, Y. Chen, N. Christensen and O. T. Keppler, "The wide utility of rabbits as models of human diseases," Experimental & Molecular Medicine 50(5): 1-10, 2018.

J. Hu, S. J. Kwon, J. J. Park, E. Landry, D. S. Mattinson and D. R. Gang, "LC-MS determination of L-DOPA concentration in the leaf and flower tissues of six faba bean (Vicia faba L.) lines with common and rare flower colors," Functional Foods in Health and Disease 5(7): 243-250, 2015.

H. Stȕtzel and M. S. Hanafy, "Impact of chitosan on shoot regeneration from faba bean embryo axes through its effect on phenolic compounds and endogenous hormones," Plant Archives 20(1): 2269-2279, 2020.

R. H. Mekky, M. M. Thabet, C. Rodríguez-Pérez, D. M. Y. Elnaggar, E. A. Mahrous, A. Segura-Carretero and E. Abdel-Sattar, "Comparative metabolite profiling and antioxidant potentials of seeds and sprouts of three Egyptian cultivars of Vicia faba L," Food Research International 136, 109537, 2020.

S. A. Fleming, A. T. Mudd, J. Hauser, J. Yan, S. Metairon, P. Steiner and R. N. Dilger, "Dietary oligofructose alone or in combination with 2′-fucosyllactose differentially improves recognition memory and hippocampal mRNA expression," Nutrients 12(7): 2131, 2020.

K. P. Skibicka, C. Hansson, E. Egecioglu and S.L. Dickson, "Role of ghrelin in food reward: impact of ghrelin on sucrose self‐administration and mesolimbic dopamine and acetylcholine receptor gene expression," Addiction Biology 17(1): 95-107, 2012.

M. F. Fernandes, S. Sharma, C. Hryhorczuk, S. Auguste and S. Fulton, "Nutritional controls of food reward," Canadian Journal of Diabetes, 37(4): 260-268, 2013.

H. Zhang and X. F. Gu, "A study of gene expression profiles of cultured embryonic rat neurons induced by phenylalanine," Metabolic Brain Disease 20(1): 61-72, 2005.

L. L. Santos, C. G. Fonseca, A. L. Starling, J. N. Januario, M. J. Aguiar, M. G. Peixoto and M. R. Carvalho,"Variations in genotype-phenotype correlations in phenylketonuria


How to Cite
Shebl, G. M., Sayed-Ahmed, H. I., Hamza, M. B., & El-Din Haider, A. S. (2021). Phenylalanine Rich Diet (Vicia faba L.) Enhances the Expression of Dopamine Receptor D3 (DRD3) Gene in Rabbits. European Journal of Biology and Biotechnology, 2(5), 81-85.