Sari Izenwasser, Ph.D.

1980     B.A.   High Honors, Psychology
            Florida International University, Miami, FL

1983     M.A.   Experimental/Physiological Psychology
            Boston University, Boston, MA

1987     Ph.D.   Experimental/Physiological Psychology
            Boston University, Boston, MA

N/A

Investigators in the Laboratory for Neuropharmacology of Drug Abuse study the effects of drugs of abuse on the brain and on behavior. Currently there are five projects receiving ongoing funding:

Neurochemical Consequences of Drug Exposure in Adolescent Rats
Source of funding:  National Institute on Drug Abuse
PI :  Sari Izenwasser, Ph.D.

The focus of this grant is to study the effects of abused substances including cocaine, MDMA (ecstasy), methylphenidate (Ritalin), and THC in adolescent rats and to examine the subsequent effects once these rats become adults.   

An understanding of the differential effects of drugs during the adolescent period and on how this use impacts drug-taking in adults may lead to different treatments for different age groups, as well as a better understanding of how drug use in adolescence may lead to psychostimulant abuse in adulthood.


Cocaine behavior: Regulation by -opioids and Serotonin
Source of funding:  National Institute on Drug Abuse
PI :  Sari Izenwasser, Ph.D.

The focus of this grant is on the effects of -opioid agonist and antagonist treatments on serotonin systems and on the effects of cocaine.   The proposed studies are both neurochemical and behavioral in nature (e.g. receptor binding and autoradiography, functional studies of dopamine uptake and release, and second messenger studies including adenylyl cyclase activity and GTPgS binding correlated with behavioral studies to determine whether any of the observed biochemical changes are physiologically relevant).


Synthesis of Potential Cocaine Abuse Therapeutics
Source of funding:  National Institute on Drug Abuse
PI :  Mark Trudell, Ph.D. (University of New Orleans) Co- Investigator:  Sari Izenwasser, Ph.D.

This project is a collaborative effort with Dr. Mark Trudell in the chemistry department at the University of New Orleans.   It involves the measurement of dopamine transporter binding and dopamine uptake of two series of compounds synthesized as potential treatments for stimulant abuse.    

Specifically, the project focuses on differential regulation of the dopamine transporter by different uptake inhibitors, especially as compared to cocaine.   These compounds have potential usefulness as treatments for disorders related to dopaminergic dysfunction.


Sex and Gender Influences on Addiction and Health:  A Developmental Perspective
Sources of funding:  National Institute on Drug Abuse; Office of Research on Women’s Health, NIH
PI:  Emmalee Bandstra, M.D., Department of Pediatrics; Co- Investigator:  Sari Izenwasser, Ph.D.

Project 2: Sex differences in Drug Effects:  The Adoelscent Trajectory
PI:  Sari Izenwasser, Ph.D.; Co- Investigator:  Ma-Li Wong, M.D.

This project is part of the Center on Addiction and Health in Women, Children and Adolescents at the University of Miami Miller School of Medicine.  The project  involves studies of the effects of nicotine, marijuana, and cocaine in adolescents.


Development of Cannabinoid Receptor Based Medications for Drug Addiction
Source of funding:  National Institute on Drug Abuse
PI : Mark Trudell, Ph.D. (University of New Orleans); Co- Investigator:  Sari Izenwasser, PhD

It has been suggested that the cannabinoid receptor system can indirectly modulate dopaminergic transmission and thus mediate the effects of psychostimulants on brain circuitry.  The aim of this project is to develop a clinically useful cannabinoid antagonist that could have application for the treatment of cannabinoid and/or psychostimulant addiction.

Books and Book Chapters

Trudell ML, Izenwasser S. (eds). Dopamine Transporters. Chemistry, Biology, and Pharmacology.  Hoboken, NJ: John Wiley & Sons, 2008.

Mash DC, Kramer LC, Izenwasser S. Dopamine transporter mRNA in human brain: distribution and regulatory effects in autopsy studies of cocaine abusers. In: Reith MEA, ed. Cerebral Signal Transduction: From First to Fourth Messengers. Totowa, NJ: Humana Press; 2000:401-417.

Izenwasser S. Basic pharmacological mechanisms of cocaine. In: Higgins S, Katz JL, eds. Cocaine abuse: Basic determinants, clinical applications, and policy. Academic Press: 1998;1-20. 

Adams JU, Izenwasser S, Kramer TH, Stevens CW, Tiseo PJ, Unterwald EM. Mechanisms of sensitization. Presentation in symposium entitled: Tolerance and sensitization to opioids and cocaine. NIDA Research Monograph, Problems of Drug Dependence. 1993;140,69-73.

Izenwasser S, Kornetsky C. Brain-stimulation reward: a method for assessing the neurochemical bases of drug-induced euphoria. In: Watson RR, ed. Drugs of Abuse and Neurobiology. Boca Raton, FL: CRC Press; 1992:1-22.

Scientific Articles in Reviewed Journals

Werling LL, Reed SC, Wade D, Izenwasser S.  Chronic nicotine alters cannabinoid-mediated locomotor activity and receptor density in periadolescent but not adult male rats. International Journal of Developmental Neuroscience, 2009, in press.

Zakharova E, Wade, D, Izenwasser S. Sensitivity to cocaine conditioned reward depends on sex and age. Pharmacology Biochemistry and Behavior. 2008;92:131-134. 

Zakharova E, Leoni G, Kichko I, Izenwasser S. Differential effects of methamphetamine and cocaine on conditioned place preference and locomotor activity in adult and adolescent male rats.  Behavioural Brain Research.  2008;198: 45-50.

Shu H, Izenwasser S, Wade D, Stevens ED, Trudell ML. Synthesis and CB₁ cannabinoid receptor affinity of 4-alkoxycarbonyl-1,5-diaryl-1,2,3-triazoles. Bioorganic Medical & Chemical Letters. 2008;19: 891-893.

Zakharova E, Collins SL, Aberg M, Kumar A, Fernandez JB, Izenwasser S. Depletion of serotonin decreases the effects of the kappa-opioid receptor agonist U-69593 on cocaine-stimulated activity. European Journal of Pharmacology. 2008;586:123-189.

Zaias J, Queeney TJ, Kelley JB, Zakharova ES, Izenwasser S. Social and physical environmental enrichment differentially affect growth and activity of preadolescent and adolescent male rats. Journal of the American Association of Laboratory Animal Science: JAALAS.  2008;47(2):30-34.

Aberg M, Wade D, Wall E, Izenwasser S. Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats. Neurotoxicology and Teratology. 2007;29:37-46.

Romualdi P, Di Benedetto M, D’Addario C, Collins S, Wade D, Candeletti S, Izenwasser S. Chronic cocaine produces decreases in N/OFQ peptide levels in select brain regions. Journal of Molecular Neuroscience. 2007;31:163-168.

D’Addario C, Di Benedetto M, Izenwasser S, Candeletti S, Romualdi P. Role of serotonin in the regulation of the dynorphinergic system by a kappa-opioid agonist and cocaine treatment in rat CNS. Neuroscience. 2007;144:163-168.

Zhang S, Izenwasser S, Wade D, Cheng J, Liu Y, Xu L, Trudell ML. Synthesis and nicotinic acetylcholine receptor affinity of bivalent tropane-3-carboxylates.  Journal of Heterocyclic Chemistry.   2007;44:1425-1430.

Zhang S, Izenwasser S, Wade D, Xu L, Trudell ML. Synthesis of dopamine transporter selective 3-(diarylmethoxymethyl)-8-arylalkyl-8-azabicyclo[3.2.1]octane derivatives. Bioorganic Medical & Chemical Letters. 2006;14:7943-7952.

Izenwasser S. Differential effects of psychoactive drugs in adolescents and adults. Critical Reviews in Neurobiology. 2005;17:51-68.

Rhoden JB, Bouvet M, Izenwasser S, Wade D, Lomenzo SA, Trudell ML. Structure-activity studies of 3’-4’-dichloro-meperidine analogues at dopamine and serotonin transporters. Bioorganic Medical & Chemical Letters. 2005;13:5623-5634.

Lomenzo SA, Rhoden JB, Izenwasser S, Wade D, Katz JL, Kopajtic T, Trudell ML. Synthesis and biological evaluation of meperidine analogues at monoamine transporters. Journal of Medical Chemistry. 2005;48:1336-1343.

Collins SL, Wade D, Ledon J, Izenwasser S. Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats. European Journal of Pharmacology. 2004;502:75-85.

Collins SL, Montano R, Izenwasser S. Nicotine treatment produces persistent increases in amphetamine-stimulated locomotor activity in periadolescent male but not female or adult male rats. Developmental Brain Research. 2004;153:175-187. 

Di Benedetto M, Feliciani D, D’Addario C, Izenwasser S, Candeletti S, Romualdi P. Effects of the selective norepinephrine uptake inhibitor nisoxetine on prodynorphin gene expression in rat CNS. Molecular Brain Research. 2004;127:115-120.

Izenwasser S. The role of the dopamine transporter in cocaine abuse. Review article. Neurotoxicity Research. 2004;6:379-384.

Winfield L, Chunming Z, Reid C, Stevens E, Izenwasser S, Wade D, Trudell ML. Synthesis, lipophilicity and structure of 2,5-disubstituted 1, 3, 5-dithiazine derivatives.  Journal of Heterocyclic Chemistry.  2003;40:827-832.

Bradley AL, Izenwasser S, Wade D, Cararas S, Trudell ML. Synthesis of dopamine transporter selective 3-{2-(Diarylmethoxy]ethylidene)}-8-alkylaryl-8-azabicyclo[3.2.1]octanes. Bioorganic & Medicinal Chemistry Letters. 2003;13:629-632.

Mash DC, Ouyang Q, Pablo J, Basile M, Izenwasser S, Lieberman A, Perrin R. Cocaine abusers have an overexpression of a-synuclein in dopamine neurons. J. Neurosci., 23:2564-71; 2003.

Izenwasser S, French D.  Tolerance and sensitization to cocaine are mediated via independent mechanisms. Pharmacological & Biochemical Behavior.  2002;73:877-882.

Collins SL, Izenwasser S.  Cocaine differentially alters behavior and neurochemistry in periadolescent vs. adult rats. Developmental Brain Research. 2002;138:27-34.

Bradley AL, Izenwasser S, Wade D, Klein-Stevens C, Zhu N, Trudell ML. Synthesis and dopamine transporter binding affinities of 3a-benzyl-8-(diarylmethoxyethyl)-8-azabicyclo[3.2.1]octanes, Bioorganic & Medicinal Chemistry Letters. 2002;12:2387-2390.

Collins SL, Kunko PM, Ladenheim B, Cadet J-L, Carroll FI., Izenwasser S. Chronic cocaine increases k-opioid receptor density: lack of effect by selective dopamine uptake inhibitors.  Synapse.  2002;45:153-158.

Cheng J, Zhang C, Stevens ED, Izenwasser S, Wade D, Chen S, Paul D, Trudell ML. Synthesis and biological evaluation at nicotinic acetylcholine receptors of N-arylalkyl- and N-aryl-7-azabicyclo[2.2.1]heptanes. Journal of Medicinal Chemistry.  2002;45:3041-3047.

Winfield L, Izenwasser S, Wade D, Trudell ML.  Synthesis and dopamine transporter binding affinity of 2,6-dioxopiperazine analogues of GBR 12909.  Medicinal Chemistry Research. 2002;11:102-115.

Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S.  Dopamine transport function is elevated in cocaine users. Journal of Neurochemistry. 2002;81: 292-300.

Schenk S, Izenwasser S.  Pretreatment with methylphenidate sensitizes rats to the reinforcing effects of cocaine. Pharmacology, Biochemistry & Behavior. 2002;72:651-657.

Xu L, Izenwasser S, Katz JL, Kopajtic T, Klein-Stevens C, Zhu N, Lomenzo SA, Winfield L, Trudell ML.  Synthesis and biological evaluation of 2-substituted 3b-tolyltropane derivatives at dopamine, serotonin, and norepinephrine transporters. Journal of Medicinal Chemistry.  2002;45:1203-1210.

Collins SL, D'Addario C, Romualdi P, Candeletti S, Izenwasser S.  Regulation of dynorphin gene expression by kappa-opioid agonist treatment.  NeuroReport.  2002;13:107-109.