Department of Pharmacology and Experimental Therapeutics

Youssef Sari, Ph.D.

Professor of Pharmacology and Vice Chair
Department of Pharmacology and Experimental Therapeutics

419.383.1507 Office
419.383.1505 Lab
419.383.1909 FAX
Frederic and Mary Wolfe Center, 282G
youssef.sari@utoledo.edu

institutions/degrees

  • B.S. Cellular Biology, Denis Diderot University (Paris, France).
  • M.S. Cellular Biology, Orsay University (Paris, France)
  • Ph.D. Neuroscience, Pierre and Marie Curie University, Institute of Neuroscience (Paris, France).
  • Postdoc and Associate Scientist: Indiana University

Research Interests

Research projects in Sari’s laboratory focus on the investigation of the role of glutamate transport in drug abuse.  While it has been clearly established that dopaminergic neurotransmission plays an important role in reward and drug addiction, we and others have shown that many aspects of the plasticity of drug dependence involves changes in glutamatergic neurotransmission.  Our laboratory is currently investigating the modulatory effects of glutamate transport in alcohol dependence, cocaine, methamphetamine, and nicotine.  Our laboratory has recently identified several FDA-approved drugs that can cross the brain blood barrier and facilitate glutamate neurotransmission.  The drugs have an upregulatory effects in key glutamate transporters such as glutamate transporter 1 (GLT-1) and cystine/glutamate antiporter (xCT).  GLT-1 is considered as a major glutamate transporter in the brain and has been clearly shown to regulate excess of extracellular glutamate in the brain. These drugs were revealed in our laboratory to upregulate GLT-1 and xCT, and consequently reduced consumption and relapse to alcohol intake as well as reduced relapse to cocaine seeking behavior in animal models.  Our laboratory has also demonstrated that these upregulators of GLT-1 and xCT can reduce nicotine consumption in animal models. Our ongoing research projects are currently investigating the pharmacological actions, pharmacokinetics, and pharmacodynamics of these drugs for the treatment of drugs of abuse.  

Publications

  1. Y. Sari, K. Lefèvre, M. Bancila, M. Quignon, M.-C. Miquel, X. Langlois, M. Hamonand D. Vergé.Light and electron microscope visualization of 5‑HT1B receptors in the rat brain. Brain Res, 1997; 760, 281-286.
  2. Y. Sari, C. Sibella, D. Vergé, M. Hamon and M-C. Miquel. Limited inhibition of 5‑HT1A receptor expression in the rat brain by antisense RNA and oligodesoxynucleotides. Neurosci Letters, 1999; 259, 191-195.
  3. Y. Sari, M.-C. Miquel, M.-J. Brisorgueil, G. Ruiz, E. Doucet, M. Hamon and D. Vergé. Cellular and subcellular localization of 5‑hydroxytryptamine1B receptors in the rat central nervous system: immunocytochemical, autoradiographic and lesion studies. Neuroscience, 1999; 88 (3), 899-915.
  4. F.C. Zhou, Y. Sari and J.K. Zhang.Expression of serotonin transporter protein in developing rat brain.Brain Res Dev Brain Res, 2000; 119 (1), 33-45.
  5. Y. Sari, T. Powrozek, F.C. Zhou. Alcohol deters the outgrowth of serotonergic neurons at midgestation. J Biomedical Sci, 2001, 8, 119-125.
  6. E.P. Riley, J.D. Thomas, C.R. Goodlett, A.Y. Klintsova, W.T. Greenough, B.L. Hungund, F.C. Zhou, Y. Sari, T. Powrozek, T.-K. Li. Fetal Alcohol Effects: Mechanisms and Treatment. Alcohol Clin Exp Res, 2001; 25(5), 110S-116S.
  7. F.C. Zhou, Y. Sari, JK. Zhang, C.R. Goodlett, T.-K. Li. Prenatal alcohol exposure retards the migration and development of serotonin neurons in fetal C57BL mice. Brain Res Dev Brain Res, 2001; 126 (2), 147-155.
  8. F.C. Zhou, Y. Sari, C.G. Goodlett, T.-K Li. Deviations in brain early serotonergic development as a result of fetal alcohol exposure. Neurotoxicity Res, 2002; 4(4), 337-342.
  9. F.C. Zhou, Y. Sari, C.R. T. Powrozek, Goodlett, T.-K. Li. Moderate alcohol exposure compromises neural tube midline development in prenatal brain. Brain Res, 2003;144, 43-55.
  10. Y. Sari, F.C. Zhou. Serotonin and its transporter on proliferation of fetal heart cells. Int J Dev Neurosci, 2003; 21(8), 417-424.
  11. Y. Sari, F.C. Zhou. Prenatal alcohol exposure causes long term serotonin neuron deficit in mice. Alcohol Clin Exp Res, 200428(6), 941-948.
  12. Y. Xu, Y. Sari, FC Zhou. Selective serotonin reuptake inhibitor disrupted the organization of thalamic afferents in rat somatosensory cortex during early postnatal development. Brain Res Dev Brain Res, 2004; 150(2), 151-161.
  13. T.A. Powrozek*, Y. Sari*, R.P. Singh*, F.C. Zhou*. Neurotransmitters and drugs of abuse: Effects on adult neurogenesis. Current Neurovascular Research, 2004; 1, 251-260. (*All authors contributed equally to this review manuscript)
  14. F.C. Zhou, Y. Sari, T. Powrozek, C.Y. Spong. A neuroprotective peptide antagonizes fetal alcohol exposure compromised brain growth. J Mol Neurosci, 2004; 24(2), 189-200.
  15. Y. Sari.  Serotonin1B Receptors: From Protein to Physiological Function and Behavior. Neuroscience and Biobehavioral Reviews, 2004; 28, 565-582.
  16. F.C. Zhou, Y. Sari, T.A. Powrozek. Fetal alcohol exposure reduces serotonin innervation and compromise development of the forebrain and the serotonergic pathway. Alcohol Clin Exp Res, 2005; 29(1), 141-149.
  17. Y. Sari, R. Bell, F.C. Zhou. Effects of continuous consumption of alcohol with and without repeated deprivations on dopamine D1 and D2 receptors in the extended amygdala of inbred alcohol-preferring rats. Alcoholism: Clin Exp Res, 2006; 30(1), 46-56.
  18. L.J. Chandler, E. Carpenter-Hyland, A. Hendricson, R. Maldve, R. Morrisett, F.C. Zhou, Y. Sari, R. Bell, K. Szumlinski. Structural and functional modifications in glutamateric synapses following prolonged ethanol exposure. Alcoholism: Clin Exp Res, 2006; 30(2), 368-376.
  19. Y. Sari, I. Gozes. Brain deficits associated with fetal alcohol exposure may be protected, in part, by peptides derived from activity-dependent neurotrophic factor and activity-dependent neuroprotective protein. Brain Res Reviews, 2006; 52(1), 107-118.
  20. F.C. Zhou, R.N. Sahr, Y. Sari, K. Behbahani. Glutamate and dopamine synaptic terminals in extended amygdala after 14-week chronic alcohol drinking in inbred alcohol-preferring rats. Alcohol, 2006; 39 (1), 39-49.
  21. B.R. Miller, J.L. Dorner, M. Shou, Y. Sari, R.T. Kennedy, G.V. Rebec. Ceftriaxone elevates GLT1 expression and improves the Huntington’s disease phenotype in R6/2 mice. Neuroscience, 2008; 153, 329-337.
  22. Y. Sari. Activity-dependent neuroprotective protein-derived peptide, NAP, preventing alcohol-induced apoptosis in fetal brain of C57BL/6 mouse. Neuroscience, 2009; 158(4):1426-1435.
  23. Y. Sari, K. Smith, A. Pir, G.V. Rebec. Up-regulation of GLT1 attenuates cue-induced reinstatement of cocaine seeking behavior in rats. J. Neuroscience, 2009, 29(29):9239-9243.
  24. Y. Sari, T. Chiba, M. Yamada, G.V. Rebec,S. Aiso. A novel peptide, colivelin, preventing alcohol-induced apoptosis in fetal brain of C57BL/6 mouse: signaling pathway investigations. Neuroscience, 2009; 164(4):1653-64.
  25. Y. Sari, M. Zhang, Y. Mechref. Differential expression of proteins in fetal brains of alcohol-treated prenatally C57BL/6 mice: a proteomic investigation. Electrophoresis, 2010; 31 (3): 483-496.
  26. Y. Sari, L.A. Hammad, M.M. Saleh, M.V. G.V. Rebec, Y. Mechref. Alteration of selective neurotransmitters in fetal brains of prenatally alcohol-treated C57BL/6 mice: quantitative analysis using liquid chromatography/tandem mass spectrometry.  Int. J. Dev. Neurosci., 2010; 28: 263-269.
  27. Y.  Sari; A. L. Prieto, S. Barton, B. R. Miller, G. V. Rebec. Regulation of GLT1 expression at multiple stages of disease progression in the R6/2 model of Huntington’s disease. J. Biomed. Sci., 2010; 17(1):62.
  28. Y. Sari, V. R.  Johnson, J.M. Weedman. Role of the serotonergic system in alcohol-drinking behavior: from animal models to clinics. Prog Mol Biol Transl Sci., 2011; 98:401-43. (Invited)
  29. Y. Sari, M. Sakai, J.M. Weedman, G.V. Rebec, R.L. Bell. Ceftriaxone, a beta lactam antibiotic, reduces alcohol consumption in alcohol-preferring rats.  Alcohol and Alcoholism, 2011; 46(3):239-46.
  30. Y. Sari. Huntington’s disease: from mutant huntingtin protein to neurotrophic factor therapy.  Int. J. Biomed. Sci., 2011; 7(2):89-100. (Invited)
  31. Y. Sari. Potential drugs and methods for preventing or delaying the progression of Huntington’s disease.Recent Pat CNS Drug Discov., 2011; 1;6(2):80-90. (Invited)
  32. Y. Sari, Z.M. Segu, A. YoussefAgha, J.A. Karty, and D. Isailovic. Neuroprotective peptide, ADNF-9, in fetal brain of C57BL/6 mice exposed prenatally to alcohol. J. Biomed. Sci., 2011; 18(1):1-12.
  33. Y. Sari, J.M. Weedman, Ge. Shufan. Activity-dependent neurotrophic factor-derived peptide prevents alcohol-induced apoptosis, in part, through Bcl2 and JNK signaling pathways in fetal brain of C57BL/6 mouse. Neuroscience, 2012; 202:465-473
  34. H.W. Nam, S.R. McIver, D.J. Hinton, M.M. Thakkar, Y. Sari, F.E. Parkinson, P.G. Haydon, and D-S. Choi. Adenosine and Glutamate Signaling in Neuron-Glial interactions: Implications in Alcoholism and Sleep Disorders. Alcoholism: Clin Exp Res, 2012; 36(7):1117-1125.
  35. Y. Kawanabe, M. Takahashi, S. Abdul-Majeed, Y. Sari, S.M. Nauli. Effect of cilostazol on extracellular calcium influx in smooth muscle contraction and proliferation. PLoS ONE, 2012;7(9):e44476
  36. P.S.S. Rao and Y. Sari. Glutamate transporter 1: target for the treatment of alcohol dependence. Current Medicinal Chemistry, 2012; 19(30):5148-5156.
  37. Y. Sari and S.N. Sreemantula. Neuroimmunophilin GPI-1046 reduces ethanol consumption in part through activation of GLT1 in alcohol-preferring rats. Neuroscience, 2012; 227: 327-335.
  38. Y. Sari. Role of 5-HT1B receptors in the regulation of Ethanol intake in rodents. J. Psychopharmacology, 2013; 27(1) 3-12.
  39. Y. Sari, J.M. Weedman, M. Nkrumah-Abrokwah. Neurotrophic peptides, ADNF-9 and NAP, prevent alcohol-induced apoptosis at midgestation in fetal brains of C57BL/6 mouse. Journal of Molecular Neuroscience, 2013;49(1), 150-156.
  40. Y. Sari,K.M. Franklin, Adnan Alazizi, P.S.S. Rao, R.L. Bell. Effects of ceftriaxone on the acquisition and maintenance of ethanol drinking in peri-adolescent and adult female alcohol-preferring (P) rats. Neuroscience, 2013; 241-229-238.
  41. Y. Sari. Experimental methods for testing the effects of neurotrophic peptide, ADNF-9, against alcohol-induced apoptosis during pregnancy in C57BL/6 mice. J Vis Exp. 2013; 24;(74). (Invited)
  42. A.M. Qrunfleh, A. Alazizi, Y. Sari. Activation of glutamate transporter 1 attenuates relapse to alcohol- seeking behavior in alcohol-preferring rats. J. Psychopharmacology, 2013; 27(6) 541-549.
  43. J. Ciesler, Y. Sari. Neurotrophic Peptides: Potential Drugs for Treatment of Amyotrophic Lateral Sclerosis and Alzheimer’s disease. Open Journal of Neuroscience, 2013; 8;3. (invited)
  44. Y.Sari. Potential therapeutic role of glutamate transporter 1 for the treatment of alcohol dependence. OA Alcohol, 2013; 1(1):6. (invited)
  45. Y. Sari, S.N. Sreemantula, Ryan Lee, and Choi D-S. Ceftriaxone attenuates alcohol intake through regulatory effects of both GLT1 and ENT1 in central reward brain regions in alcohol-preferring rats. Journal of Molecular Neuroscience, 2013; 51(3):779-87.
  46. P.S.S. Rao, Y. Sari. Effects of ceftriaxone on chronic ethanol consumption: a potential role for xCT and GLT1 modulation of glutamate levels in male P rats. Journal of Molecular Neuroscience, 2014; 54 (1) 71-77.
  47. A. Schneider, Y. Sari. Potential trophic factors and drugs for alleviating the symptoms of Alzheimer’s disease. CNS Neurol Disord Drug Targets, 2014; 13: 909-920.
  48. T. Liu, X. Jin, R. Prasad, Y. Sari, and S. Nauli. Three distinct types of ependymal cells with intracellular calcium oscillation property. Journal of Neuroscience Research, 2014; 92(9):1199-11204.
  49. H. Alhaddad, Sujan Das, Y. Sari. Effects of ceftriaxone in ethanol-drinking behavior: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats. Psychopharmacology, 2014; 231(20):4049-4057.
  50. G. Yacila, Y. Sari. Potential drugs and methods for attenuating or treating amyotrophic lateral sclerosis. Current Medicinal Chemistry, 2014; 21(31):3583-93. (Invited)
  51. Y. Sari. Role of glutamate transporter 1 in the attenuation of alcohol intake. Frontiers in Neuroscience, 2014; 17;8:200.
  52. H. Alhaddad, M. Aal-Aaboda, Y.S. Althobaiti, S.H.S. Boddu, Y. Wei, N. Kim, J. Leighton, Y. Sari. Effects of MS-153 on chronic ethanol consumption and GLT1 modulation of glutamate levels in male alcohol-preferring rats. Frontiers in Behavioral Neuroscience, 2014; 8:366.
  53. S.R. Hauser, P.B. Hedlund, A.J. Roberts, Y. Sari, R.L. Bell, and E.A. Engleman. The 5-HT-7 receptor as a potential target for treatment of drug and alcohol abuse. Frontiers in Neuroscience, 2015; 8:448.
  54. P.S.S. Rao, Y. Sari. Effectiveness of ceftriaxone treatment in preventing relapse-like drinking behavior following long-term ethanol dependence in P rats. Journal of Addiction Research and Therapy, 2014; 5.
  55. M. Rinaldi, A.C. Johann, F. Rocha, S.A. Ignacio, E.A. Rosa, L.R. Alanis, Y.Sari, S. da Silva, A.A. de Lima,  A.M. do Prado, P.V. Bettega, A.M. Gregio. Histomorphometric analysis of salivary gland in Wistar treated chronically with two benzodiazepines. Current Pharmaceutical Biotechnology, 2015; 16(6):573-578.
  56. P.S.S. Rao, S. Goodwani, R.L. Bell, Y. Wei, S. Boddu, and Y. Sari. Effects of ampicillin, cefazolin and cefoperazone treatments on GLT1 expressions in the mesocorticolimbic system and ethanol intake in alcohol-preferring rats. Neuroscience, 2015; 4;295: 164-174.
  57. M. Aal-Aaboda, H. Alhaddad, F. Osowik, S. M. Nauli, and Y. Sari.Effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1 and cysteine/glutamate exchanger as well as ethanol drinking behavior in male, alcohol-preferring rats. Journal of Neuroscience Research, 2015; 93(6):930-937.
  58. P.S.S. Rao, R.L. Bell and E.A. Engleman, Y. Sari. Targeting glutamate uptake to treat alcohol use disorders. Front Neurosci. 2015; 23;9:144.
  59. F. Alasmari, S. Abuhamdah and Y. Sari. Effects of ampicillin on cysteine/glutamate exchanger transporter and glutamate transporter 1 isoforms as well as ethanol drinking behavior in male P rats. Neurosci Lett. 2015; 10;600:148-152.
  60. S. C. Das, B. K. Yamamoto, A. M. Hristov, and Y. Sari.Ceftriaxone attenuates ethanol drinking and restores extracellular glutamate level through normalization of GLT-1 in NAc of male alcohol-preferring (P) rats. Neuropharmacology, 2015; 19; 97:67-74.
  61. P.S.S. Rao, H. Saternos, S. Goodwani, and Y. Sari. Effects of ceftriaxone on GLT1 isoforms, xCT and associated signaling pathways in P rats exposed to ethanol. Psychopharmacology, 2015; 232(13):2333-42.
  62. Y. Sari and A. Khalil. Monoamine oxidase inhibitors extracted from tobacco smoke as neuroprotective factors for potential treatment of Parkinson’s disease. CNS Neurol Disord Drug Targets, 2015; 14(6):777-85.
  63. S. Goodwani, P.S.S. Rao, R. L. Bell, and Y. Sari. Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT1 expression as well as AKT phosphorylation in mesocorticolimbic regions. Brain Research, 2015; 1622: 397-408.
  64. P.S.S. Rao, M. M. Yallapu, Y. Sari, P. B. Fisher, and S. Kumar. Designing novel nanoformulations targeting glutamate transporter 1/excitatory amino acid transporter 2: implications in treating drug addiction. Journal of Personalized NanoMedicine, 2015; 1(1):3-9.
  65. F. Alasmari, S.S. Al-Rejaie, S.D. Al-Sharari,and Y. Sari. Targeting glutamate homeostasis for potential treatment of nicotine dependence. Brain Research Bulletin, 2016; 121:1-8.
  66. S.C. Das, Y.S. Althobaiti, F.S. Alshehri, Y. Sari.Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model. Behavioral Brain Research, 2016; 25, 303:120-125.
  67. R.L. Bell, S. Hauser, Z.A. Rodd, T. Liang, Y. Sari, J. McClintick, S. Rahman, and E.A. Engleman. A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction.  International Review of Neurobiology, 2016; 126:179-261.
  68. F. Alasmari, P.S.S. Rao and Y. Sari. Effects of cefazolin and cefoperazone on glutamate transporter 1 isoforms and cystine/glutamate exchanger as well as alcohol drinking behavior in male alcohol-preferring rats. Brain Research, 2016; 1, 1634:150-157.
  69. Y. Sari,J.E. Toalston, P.S.S. Rao, and R. L. Bell. Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT1 expression. Neuroscience, 2016; 326:117-125.
  70. S. Abuhamdah, A. Khalil and Y. Sari. Targeting dopaminergic system for treating nicotine dependence. Central Nervous System Agents in Medicinal Chemistry, 2016; 16, 1-6.
  71. A. Hakami, A. Hammadand Y. Sari. Effects of amoxicillin and Augmentin on cystine-glutamate exchanger and glutamate transporter 1 isoforms as well as Ethanol Intake in Alcohol-Preferring Rats. Frontiers in Neuroscience, 2016; 25, 10:171.
  72. T.M.F. Mattioli, L.R. de Azevedo Alanis, S.S. Sapeli, A.A.S. de Lima, L. Noronha, E.A.R. Rosa, Y.S. Althobaiti, A.H. Almalki, Y. Sari, S.A. Ignacio, A.C.B. Johann, and A.M.T. Grégio. Effects of Benzodiazepines on Acinar and Myoepithelial Cells. Frontiers in Neuroscience, 2016; 7: 173.
  73. Y.S. Althobaiti and Y. Sari. Alcohol interactions with psychostimulants: an overview of animal and human studies. Journal of Addiction Research and Therapy, 2016; 7:3.
  74. N. Patel, D. Lalwani, S. Gollmer, E. Injeti, Y. Sari, and J. Nesamony. Development and Evaluation of a Calcium Alginate based Oral Ceftriaxone Sodium Formulation. Progress in Biomaterials, 2016; 5:117-133.
  75. Y.S. Althobaiti, F.S. Alshehri, A. H. Almalki, and Y. Sari. Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered ethanol and methamphetamine.  Frontiers in Neuroscience, 2016; 10, 427.
  76. Y.S. Althobaiti, A.H. Almalki, S.C. Das, F.S. Alshehri, and Y. Sari. Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on dopamine and serotonin tissue content as well as glutamate-glutamine cycle. Neuroscience Letters, 2016; 634, 25-31.
  77. F.F. Veiga, A.C. Johann, V. da Silva Kagy, L.T. Muniz, L.A. Alanis, E.A. Rosa, S.A. Ignacio, A.A. de Lim, S. Abuhamadah, Y.S. Althobaiti, Y. Sari, A.P. Martins, and A.M.T. Grégio. "Action of lithium carbonate on parotid acini." Dental, Oral and Craniofacial Research, 2016; 2(3):287–288.
  78. A.Y. Hakami, F.S. Alshehri,Y.S. Althobaiti, and Y. Sari. Effect of oral Augmentin on glutamate transporter 1, cystine-glutamate exchanger expression as well as Ethanol Intake in Alcohol-Preferring Rats. Behavioural Brain Research, 2017; 320-316-322.
  79. Y. Sari. Commentary: Targeting NMDA receptor and serotonin transporter for the treatment of comorbid alcohol dependence and depression. Alcohol Clin Exp Res. 2017; 41(2):275-278.
  80. F.S. Alshehri, Y.S. Althobaiti, Y. Sari. Effects of administered ethanol and methamphetamine on Glial glutamate transporters in Rat Striatum and Hippocampus. J. Mol. Neurosc., 2017, 61(3):343-350.
  81. R.L. Bell, S.R. Hauser, T. Liang, Y. Sari, A. Maldonado-Devincci , and Z.A. Rodd. Rat animal models for screening medications to treat alcohol use disorders. Neuropharmacology, 2017, 1; 122:201-243.
  82. S. Goodwani, H. Saternos, F. Alasmari, and Y. Sari. Metabotropic and ionotropic glutamate receptors as potential targets for the treatment of alcohol use disorder.  Neuroscience and Biobehavioral Reviews, 2017, 77-14-31.
  83. F. Alasmari, L. C. Alexander, J. A. Nelson, I.T. Schiefer, E. Breen, C. A. Drummond, and Y. Sari. Effects of chronic inhalation of electronic cigarettes containing nicotine on the glutamatergic system in female CD-1 mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2017, 77, 1-8.
  84. A.M. Hammad, Y.S. Althobaiti, S.C. Das, and Y. Sari. Effects of repeated cocaine exposure and withdrawal on voluntary ethanol drinking, and the expression of glial glutamate transporters and metabotropic glutamate receptors in mesocorticolimbic system in P rats.  Molecular and Cellular Neuroscience, 2017, 22;82:58-65.
  85. A.M. Hammad, F. Alasmari, Y.S. Althobaiti, and Y. Sari. Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine seeking behavior. Behavioural Brain Research, 2017, 82:58-65.
  86. A.Y. Hakami and Y. Sari. β-lactamase inhibitor, clavulanic acid, attenuates ethanol intake and increases glial glutamate transporters expression in alcohol preferring rats. Neuroscience Letters, 2017, 657C, 140-145.
Last Updated: 8/23/17