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Koek, Wouter

School of Medicine
Psychiatry
(210) 567-5480
koek@uthscsa.edu

Wouter Koek, Ph.D., obtained a bachelor degree in psychology, a masters degree in physiological psychology and statistics, and a Ph.D. in behavioral pharmacology from the University of Utrecht, The Netherlands. After post-doctoral training in the Department of Pharmacology of the University of Michigan, he worked fifteen years in the pharmaceutical industry (Institut de Recherche Servier, France; Pierre Fabre Medicament; France) to conduct drug discovery research aimed at developing new treatments for psychiatric disorders. In 2002, he joined the faculty in the Division of Alcohol and Drug Addiction, with a joint appointment in the Department of Pharmacology. In 2005, Dr. Koek was appointed to the endowed START Center Medication Research Professorship.

Dr. Koek divides his time between research, education, and service. He conducts preclinical research using animal models relevant to alcohol and drug abuse. His studies examine how genetic factors, developmental factors, and their interaction influence vulnerability to drug abuse and other psychiatric disorders. This research, which is supported by NIH, NIAAA, and NARSAD, is aimed at contributing to the development of effective, scientifically based approaches to the prevention and treatment of these disorders.

Dr. Koek is invested in student education in the Departments of Psychiatry and Pharmacology. His educational efforts draw on his extensive experience with pharmaceutical drug discovery research, and on his experience with research- and statistical methods.

Dr. Koek is involved in several scientific societies and editorial boards of international scientific journals. He is a member of national and international scientific societies such as the American College of Neuropsychopharmacology, the Committee on Problems of Drug Dependence, the American Society for Pharmacology and Experimental Therapeutics, and the Behavioral Pharmacology Society.

Appointments Education Expertise Teaching Publications Grants

9/2009 - Present	Professor	University of Texas Health Science Center at San Antonio, Psychiatry
2/2005 - Present	endowed START Center Medication Research Professorship	University of Texas Health Science Center at San Antonio, Psychiatry

1) Animal models of alcohol and drug abuse

- My work involves using and developing animal models that can be used to identify medications for substance abuse. In addition to medication development, the models are also used in studies aimed at examining the etiology of drug abuse, and its underlying mechanisms.The models involve behavioral effects that range from directly observable effects (e.g., drug-induced motor impairment) to effects examined by conditioning procedures (e.g., conditioned place preference, which is related to rewarding effects of drugs, and discriminative stimulus effects, which are related to subjective drug effects in humans).

2) Etiology of drug and alcohol abuse

- Many people drink and/or use drugs recreationally, particularly during adolescence, but only some become addicted. Genetic factors likely play a role, but environmental factors may also be involved. To study interactions between genetic make-up and environmental conditions, models in mice are especially useful. Initiation of drug abuse occurs primarily during adolescence, and during this developmental period alcohol and drugs of abuse may have distinct effects that could increase risk for abuse. In mice, adolescence has been defined as spanning from postnatal days 28-42. Thus, procedures useful to study drug effects during adolescence in mice have to be rapid enough to be conducted within a two-week period. One of the current priorities in my lab is the development of rapid behavioral procedures suitable to examine developmental aspects of abuse related drug effects in mice, the species of choice for the experimental study of gene-environment interaction. These procedures will be used to learn more about risk factors for the abuse of alcohol and for the rising abuse of prescription opioid analgesics by adolescents. This research, which is supported in part by an NIH grant (NIAAA), and by the START Center Medication Development Endowment, will increase our understanding of risk factors for alcoholism and drug abuse, and will help the development of effective approaches to prevention and treatment.

3) Mechanistic studies

- The pharmacological mechanisms by which drugs produce their abuse-related effects are, for the most part, poorly understood. Abuse potential of a particular drug is likely related to its subjective effects, and subjective effects of drugs in humans can often be predicted from drug discrimination experiments in animals. The discriminative stimulus effects of most drugs involve several different receptor mechanisms; some of which may be unique to that drug and some which are common with other drugs. Current efforts, supported by an NIH grant (NIDA), are aimed at understanding the mechanism of action of gamma-hydroxybutyrate (GHB). GHB is abused primarily by adolescents and young adults, and is often taken together with alcohol and with other club drugs such as ketamine. Abuse of such drugs continues to play a major role in the spread of HIV, by altering judgment that leads to impulsive high-risk sex. By identifying the role of specific receptors in abuse, future studies may be better able to develop specific, pharmacologically targeted therapies for drugs of abuse.

4) Drug discovery and development

- I have worked for 15 years in the pharmaceutical industry, where I have directed drug discovery projects aimed at identifying novel treatments for central nervous system disorders. My experience in industry benefits UTHSCSA in at least two ways. First, it helps me teaching Psychiatry residents to critically evaluate studies that claim effectiveness and superiority of novel drugs acting on the central nervous system. Second, having experience both in the pharmaceutical industry and in academia enables me to provide graduate students with a balanced but experienced first-hand perspective of both settings. Graduate students are generally more nave about research in industry than in academia. Learning about research in industry widens career opportunities for students, and may help to meet the pressing and currently unmet need for scientists in the biopharmaceutical industry. Teaching about industrial research by offering a formal program in Drug Discovery and Development would fill an important void and would give UTHSCSA a competitive edge, because at present only one university in the USA that is taking steps to initiate such a training program.

Date	Description	Institution	# Students
6/2011 - 6/2015	Ph.D. Dissertations Directed	UTHSCSA

3/2010 - Present	Membership on Supervising Committee

3/2010 - Present	Membership on Supervising Committee

1/2010 - Present	Drug Discovery and Development Committee (Chair)
The mission of this subcommittee of the Education Committee of the Department of Pharmacology is to explore various options for a drug discovery and development program.
1/2008 - Present	Special Topics: Microelectives	The University of Texas Health Science Center
Course Director - This course, entitled "Drug Discovery: Nuts and Bolts", is aimed at familiarizing graduate students with the history of drug discovery, its current status, and future directions. Students are generally more naive about research in industry than in academia. The aim of this course is to provide an opportunity to learn about research in industry. This course could provide a basis for a more extensive training program in Drug Discovery and Development. There are many reasons to initiate such a program, such as the pressing and currently unmet need for scientists in the biopharmaceutical industry, and the considerable interest of students to learn about a career in industry versus a career in academia.
6/2007 - Present	Journal Club Psychiatry Residents
The journal club teaches residents to critically evaluate clinical studies. I specifically help residents to examine studies that claim effectiveness and superiority of novel drugs acting on the central nervous system. Having worked for 15 years as CNS drug discovery researcher in the pharmaceutical industry helps me to teach a critical approach to such studies.
4/2007 - Present	Drug Development Initiative Group	UTHSCSA
Requested by Dr. Alan Frazer, Chair of Pharmacology, and Dr. Bruce Nicholson, Chair of Biochemistry, I give a seminar on current approaches to drug discovery and development, based on my experience in the pharmaceutical industry. This seminar is aimed at helping to explore opportunities for medicinal chemistry at UTHSCSA.
11/2006 - Present	Seminar on Careers in Biomedical Sciences	Our Lady of the Lake University	10 students
This seminar is aimed at helping undergraduates decide their career. The seminar compares and contrasts biomedical research in industry and in academia, based on my experience in both work environments. Both provide many opportunities for scientific collaborations.
9/2006 - Present	Research Methods in Psychiatry
This course is aimed at teaching residents research methods in Psychiatry. I help them evaluate the usefulness of diagnostic tests, using concepts such as sensitivity and specificity. In addition to providing an overview of commonly used statistical tests, I focus on randomization tests, which are easy to understand, simple to compute, and especially useful in single case and small-n studies. Knowing how to apply these tests helps clinicians to evaluate, in a variety of settings including private practice, the effectiveness of interventions.
8/2006 - Present	Substance Abuse Seminars for PG1 residents
This course teaches residents about substance use disorders and substance-induced disorders. I focus on stimulants, hallucinogens, phencyclidine and related drugs (e.g., ketamine), prescription drugs and over-the-counter medicines, inhalants, and, with the help of Dr. Brett Ginsburg, on cannabis. The emphasis is on the acute and chronic effects of these drugs, and on possible treatments.
6/2004 - Present	Research Methods in Psychiatry
Based on my experience in the pharmaceutical industry, I teach residents current approaches to discover and develop novel drugs for the treatment of central nervous system disorders. Knowledge about the drug discovery and development process helps residents to critically evaluate results of clinical studies with novel drugs.
8/2003 - Present	Psychiatry Grand Rounds
Based on my experience in the pharmaceutical industry, I teach residents current approaches to discover and develop novel drugs for the treatment of central nervous system disorders. Knowledge about the drug discovery and development process helps residents to critically evaluate results of clinical studies with novel drugs.
1/2003 - Present	Pharmacology Seminar	The University of Texas Health Science Center
I give seminars for the Pharmacology Department that describe current approaches to drug discovery and development. Although graduate students have ample opportunity to familiarize themselves with research in academia, the same is not true for research in industry. The seminars are aimed at providing graduate students with a general introduction to research in the pharmaceutical industry. To provide more detail about drug discovery, I offer an additional course that is part of the Pharmacology Graduate Program.
6/2002 - Present	Biological Bases of Brain Function
As part of the summer undergraduate research program of the Department of Pharmacology, I give seminars that teach undergraduates about substance use disorders, their underlying mechanisms, and the animal models used to study these mechanisms. The overall aim is to help undergraduates decide to pursue an advanced degree and a career in the biomedical sciences.

Journal Article

Koek W, France CP, Cheng K, Rice KC. Effects of the GABAB receptor-positive modulators CGP7930 and rac-BHFF in baclofen- and ?-hydroxybutyrate-discriminating pigeons J Pharmacol Exp Ther 2012 May;341(2):369-376.

Koek W, France CP, Javors MA. Morphine-induced motor stimulation, motor incoordination, and hypothermia in adolescent and adult mice Psychopharmacology (Berl) 2012 Feb;219(4):1027-1037.

Hensler JG, Advani T, Burke TF, Cheng K, Rice KC, Koek W. GABAB receptor positive modulators: brain region-dependent effects Journal of Pharmacology and Experimental Therapeutics 2011 Sep;.

Koek W. Drug-induced state-dependent learning: review of an operant procedure in rats Behav Pharmacol 2011 Jun;.

Li J, Koek W, Rice KC, France CP. Effects of direct- and indirect-acting serotonin receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in rhesus monkeys Neuropsychopharmacology 2011 Apr;36(5):940-949.

Assie M-B, Bardin L, Auclair AL, Carilla-Durand E, Depoortere R, Koek W, Kleven MS, Colpaert FC, Vacher B,Newman-Tancredi A. F15599, a highly selective postsynaptic 5-HT1A receptor agonist: in vivo profile in behavioural models of antidepressant and serotonergic activity International Journal of Neuropsychopharmacology 2010 Nov;13(10):1285-1298.

Koek W, France CP, Cheng K, Rice KC. GABA(B) receptor positive modulators: enhancement of GABA(B) receptor agonist effects in vivo Journal of Pharmacology and Experimental Therapeutics 2010 Oct;335(1):163-171.

Li J-X, Koek W, Rice KC, France CP. Differential effects of 5-HT1A receptor agonists on the discriminative stimulus effects of the 5-HT2A agonist DOM in rats and rhesus monkeys Journal of Pharmacology and Experimental Therapeutics 2010 Apr;333(1):244-252.

Becker G, Gerak LR, Li J, Koek W, France CP. Precipitated and conditioned withdrawal in morphine-treated rats Psychopharmacology 2010 Jan;209:85-94.

Li J, Koek W, Rice KC, France CP. Differential effects of 5-HT1A receptor agonists on the discriminative stimulus effects of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rats and rhesus monkeys Journal of Pharmacology and Experimental Therapeutics 2010 Jan;333:244-252.

Li JX, Unzeitig A, Javors M, Rice KC, Koek W, France CP. Discriminative stimulus effects of DOM, ketanserin, and MDL100907 in rats Journal of Pharmacology and Experimental Therapeutics 2009 Nov;331(2):671-679.

Koek W, Mercer SL, Coop A, France CP. Behavioral effects of GHB, its precursor GBL, and GABA(B) receptor agonists: time course and differential antagonism by the GABA(B) receptor antagonist CGP35348 Journal of Pharmacology and Experimental Therapeutics 2009 Sep;330(3):876-883.

France CP, Li J-X, Owens WA, Koek W, Toney GM, Daws LC. Reduced effectiveness of escitalopram in the forced swimming test is associated with increased serotonin clearance rate in food restricted rats Int J Neuropsychopharmacol 2009 Jul;12(6):731-736.

Li JX, Koek W, France CP. Food restriction and streptozotocin differentially modify sensitivity to the hypothermic effects of direct- and indirect-acting serotonin receptor agonists in rats European Journal of Pharmacology 2009 Apr;.

Advani T, Koek W, Hensler JG. Gender differences in the enhanced vulnerability of BDNF+/- mice to mild stress International Journal of Neuropsychopharmacology 2009 Apr;:1-6.

Carter LP, Koek W, France CP. Behavioral analyses of GHB: receptor mechanisms Pharmacology & Therapeutics 2009 Jan;121:100-114.

Li J, Unzeitig A, Javors MA, Rice KC, Koek W, France CP. Discriminative stimuls effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), ketanserin, and (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907) in rats Journal and Pharmacology and Experimental Therapeutics 2009 Jan;331:671-679.

Koek W, Mercer SL, Coop A, France CP. Behavioral effects of gamma-hydroxybutyrate, its precursor gamma-butyrolactone, and GABA(B) receptor agonists: time course, and differential antagonism by the GABA(B) receptor antagonist 3-aminopropyl (diethoxymethyl) phosphinic acid (CGP35348) Journal of Pharmacology and Experimental Therapeutics 2009 Jan;330:876-883.

Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC. Organic cation transporter 3: keeping the brake on extracellular serotonin in serotonin transporter deficient mice Proceedings of the National Academy of Sciences 2008 Dec;105(48):18976-18981.

Sevak RJ, Koek W, Owens WA, Galli A, Daws LC, France CP. Feeding conditions differentially affect the neurochemical and behavioral effects of dopaminergic drugs in male rats Eur J Pharmacol 2008 Sep;592(1-3):109-115.

Koek W, France CP. Cataleptic effects of y-hydroxybutyrate (GHB) and baclofen in mice: mediation by GABAB receptors, but differential enhancement of N-methyl-d-aspartate (NMDA) receptor antagonists Psychopharmacology 2008 Apr;199:191-198.

Sevak RJ, Koek W, Daws LC, Owens WA, Galli A, France CP. Behavioral effects of amphetamine in streptozotocin-treated rats European Journal of Pharmacology 2008 Feb;581:105-112.

Becker GL, Gerak LR, Koek W, France CP. Antagonist-precipitated and discontinuation-induced withdrawal in morphine-dependent rhesus monkeys Psychopharmacology 2008 Jan;201:373-382.

Koek W, Khanal M, France CP. Synergistic interactions between "club drugs": gamma-hydroxybutyrate (GHB) and phencyclidine (PCP) enhance each others discriminative stimulus effects Behavioural Pharmacology 2007 Nov;18:807-810.

Advani T, Hensler JG, Koek W. Effect of early rearing conditions on alcohol drinking and 5-HT1A receptor function in C57BL/6 mice International Journal of Neuropsychopharmacology 2007 Oct;10:595-607.

Boctor SY, Martinez JL, Koek W, France CP. The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding European Journal of Pharmacology 2007 Sep;571:39-43.

McMahon LR, Koek W. Differences in the relative potency of SR 141716A and AM 251 as antagonists of various in vivo effects of cannabinoid agonists in C57BL/6J mice Eur J Pharmacol 2007 Aug;569(1-2):70-76.

Colpaert FC, Koek W, Kleven MS, Besnard J. Induction by antipsychotics of "win-shift" in the drug discrimination paradigm Journal of Pharmacology and Experimental Therapeutics 2007 Jul;322:288-298.

Abstract

Koek W. Sensitization of morphine-induced motor stimulation: age-related differences in mice; 2012 Apr. (ASPET meeting).

Apple D, Horton RE, Baganz NL, Cano S, Owens WA, Vitela M, Gould GG, Koek W, Daws LC. Decynium-22 enhances SSRI-induced antidepressant effects in mice: uncovering new targets to treat depression; 2012 Apr. (ASPET meeting).

Hensler JG, Advani T, Burke TF, Cheng K, Rice KC, Koek W. Brain region-dependent effects of GABA-B receptor positive modulators; 2011 Nov. (Soc Neurosci Program; vol. 233, no. 02).

Apple DM, Cano SA, Horton RE, Vitela M, Koek W, Daws LC. Decynium-22, an organic cation transporter 3 blocker, inhibits serotonin uptake in hippocampus and exerts antidepressant-like effects in mice; 2011 Nov. (Neuroscience meeting).

Koek W, France CP, Cheng K, Rice KC. GABA-B receptor positive modulators: differential enhancement of the discriminative stimulus effects of baclofen and gamma-hydroxybutyrate (GHB); 2011 Jun. (CPDD meeting).

Koek W. Morphine-induced motor stimulation after repeated administration: age-related differences in mice; 2011 Jun. (INRC meeting).

Koek W, France CP, Cheng K, Rice KC. Effects of positive GABA-B receptor modulators in pigeons trained to discriminate baclofen or gamma-hydroxybutyrate (GHB) from saline; 2011 Apr. (ASPET meeting).

Koek W, France CP, Javors MA. Morphine-induced motor stimulation and ataxia: age-related differences in mice; 2011 Apr. (ASPET meeting).

Koek W, France CP, Cheng K, Rice KC. Effects of the positive GABA-B receptor modulators, CGP7930 and rac-BHFF, in animals trained to discriminate baclofen or gamma-hydroxybutyrate (GHB) from saline; 2010 Dec. (ACNP meeting).

Baganz, N.L., Horton, R.E., Koek,W. and Daws, L.C. Organic Cation Transporter 3: The Culprit Undermining Therapeutic Utility of SSRIs?; 2010 Dec. (American College of Neuropsychopharmacology).

McMahon LR, Koek W. Bupropion exerts cannabinoid antagonist activity in rhesus monkeys; 2010 Dec. (ACNP meeting).

Hensler JG, Koek W, Daws LC. BDNF deficient mice: a model of changes associated with an increased susceptibility to depression; 2010 Jul. (Serotonin Club Meeting).

Koek W, France CP. Morphine-induced motor stimulation and motor incoordination: age-related differences in mice; 2010 Jun. (CPDD meeting).

Koek W, France CP. Morphine-induced motor stimulation and ataxia: differences among adolescent, late adolescent, and adult mice; 2010 Apr. (ASPET meeting).

Advani T, Hensler JG, Cheng K, Rice KC, Koek W. Stimulation of [35S]GTPgammaS binding by GABAB receptor agonists and positive modulators in different brain regions; 2010 Apr. (ASPET meeting).

Koek W, France CP, Cheng K, Rice KC. The positive GABA-B receptor modulators, CGP7930 and rac-BHFF, enhance behavioral effects of baclofen and gamma-hydroxybutyrate (GHB); 2009 Dec. (ACNP Meeting).

Campos PS, Gould GG, Alvarado SS, Baganz N, Koek W, Daws LC. Developmental changes in hippocampal SERT expression and function and effect of antidepressant drugs in mice with constitutively reduced SERT expression; 2009 Nov. (Society for Neuroscience Meeting).

Koek W, France CP, Cheng K, Rice KC. Effects of CGP7930, a GABA-B receptor positive modulator, on baclofen- and GHB-induced hypothermia and loss of righting in mice; 2009 Sep. (European Behavioural Pharmacology Society (EBPS) Meeting).

France CP, Li JX, Koek W, Rice KR. 5-HT and opioid drug interactions in rats and monkeys: drug discrimination; 2009 Sep. (European Behavioural Pharmacology Society (EBPS) Meeting).

Koek W, Campos PS, France CP, Cheng K, Rice KC. GHB- and baclofen-induced hypothermia in mice: interactions with the GABA-B receptor positive modulator CGP7930, the GABA-B receptor antagonist CGP35348, and the NOS inhibitor L-NAME; 2009 Jun. (CPDD meeting).

Li JX, Rice KC, Koek W, France CP. Differential modification of the antinociceptive and discriminative stimulus effects of morphine by 5-HT1A and 5-HT2A receptor agonists in rhesus monkeys; 2009 Jun. (CPDD meeting).

Hensler JG, Daws LC, Koek W. Brain-derived neurotrophic factor (BDNF) deficient mice: a model of predisposition to depression; 2009 May. (Stress and Behavior Conference).

Li J-X, Rice KC, Koek W, France CP. Discriminative stimulus effects of DOM in rhesus monkeys: interactions between 5-HT1A and 5-HT2A receptor agonists; 2009 Apr. (ASPET meeting).

Koek W. Discriminative stimulus effects of alcohol: a rapid training procedure in mice; 2009 Feb. (TRSA meeting).

Hensler JG, Daws LC, Koek W. Brain-derived neurotrophic factor (BDNF) deficient mice: a model of predisposition to depression; 2009 Jan. (Multidisciplinary International Conference of Neuroscience and Biological Psychiatry).

Koek W, Campos PS, Cheng K, Rice KC, France CP. CGP7930, a positive modulator of GABA-B receptors, enhances catalepsy induced by the GABA-B receptor agonist baclofen and by gamma-hydroxybutyrate (GHB), and produces hypothermia when given alone; 2008 Dec. (ACNP meeting).

Baganz NL, Horton RE, Owens WA, Koek W, Toney GM, Daws LC. Organic cation transporters: the answer to the unsertainty of antidepressant response revealed?; 2008 Jul. (EPHAR Meeting 2008).

Hensler JG, Advani T, Koek W. BDNF+/- mice exhibit region-specific decreases in 5-HT1A receptor function and increased vulnerability to mild handling stress; 2008 Jul. (Presented at the 2nd EPHAR Serotonin Satellite Meeting).

Koek W, Cheng K, Rice KC, France CP. CGP7930, a positive modulator of GABA-B receptors, enhances catalepsy induced by the GABA-B receptor agonist baclofen and by gamma-hydroxybutyrate (GHB); 2008 Jun. (CPDD meeting).

Koek W, Hidalgo JA, Daws LC. The anti-cataleptic effects of 8-OH-DPAT: role of pre-synaptic 5-HT1A receptors, and possible implications for combined treatment with antidepressants and antipsychotics; 2008 Apr. (ASPET meeting).

Sevak RJ, Koek W, Owens WA, Galli A, Daws LC, France CP. Effects of food restriction on dopamine clearance and behavioral effects of dopaminergic drugs in rats; 2008 Apr. (ASPET meeting).

Baganz NL, Horton RE, Owens WA, Koek W, Toney GM, Daws LC. Organic cation transporter 3: a novel target for antidepressant medications; 2008 Mar. (American Society for Neurochemistry Meeting 2008).

Daws L, Baganz NL, Horton RE, Toney GM, Koek W. Organic cation transporters: a target for the development of novel antidepressants; 2007 Dec. (ACNP Meeting).

Koek W, Hidalgo JA, Daws LC. The anti-cataleptic effects of the 5-HT1A receptor agonist 8-OH-DPAT depend on the expression level of the serotonin transporter: possible implications for combined treatment with antidepressants and antipsychotics; 2007 Dec. (ACNP Meeting).

D.A. Price, W. Koek, J.L. Roberts and A. Giuffrida. Neuroprotective effects of cannabinoids in a mouse model of Parkinson''s disease; 2007 Nov. (37th Society for Neuroscience Meeting, San Diego).

Advani T, Koek W, Hensler JG. Interaction of stress and a deficiency in brain derived neurotrophic factor: a putative mouse model of depression; 2007 Oct. (Neuroscience 2007).

Koek W, France CP. Gamma-hydroxybutyrate (GHB): receptor mechanisms; 2007 Sep. (European Behavioural Pharmacology Society (EBPS) Meeting).

Federal
Funding Agency	ASPET
Title	ASPET Fellowship Program for Undergraduate Students
Status	Active
Period	6/2007 - Present
Role	Contributor
Grant Detail
Funding Agency	NIH
Title	Delay Discounting: Effects of Drug Dependence and Withdrawal
Status	Active
Period	7/2010 - 6/2015
Role	Co-Investigator
Grant Detail
Funding Agency	NIH/NIDA
Title	Discriminative Stimulus Effects of Opioid Withdrawal
Status	Active
Period	2/2010 - 1/2015
Role	Co-Investigator
Grant Detail	Investigate opioid dependence and withdrawal in monkeys and pigeons using drug dependence procedures in order to identify and characterize novel pharmacotherapeutic approaches for the treatment of opioid abuse.
Funding Agency	NIH/NIDA
Title	Neurobiology of GHB Discrimination - Competitive Renewal
Status	Active
Period	9/2007 - 8/2012
Role	Principal Investigator
Grant Detail	To increase our understanding of the interactions between the glutamatergic system, which is thought to play an important role in modulating/mediating effects of drugs of abuse, and the systems (GHB, GABA) involved in the behavioral effects of GHB. The contributions of these studies extend beyond substance abuse to questions about the mechanisms of GHB that contribute to its therapeutic actions, about the physiological role of the endogenous GHB system, and about interactions between this system and the glutamatergic system. Increased knowledge about the GHB system will help to develop scientifically-based, effective approaches to treating sleep-, drug abuse-, and other CNS disorders.
Funding Agency	NIH/NIMH
Title	Mechanisms regulating serotonin clearance in vivo: studies using KO mice
Status	Active
Period	7/2007 - 6/2012
Role	Co-Investigator
Grant Detail	The goal of these studies is to determine how mechanisms that control clearance of serotonin from extracellular fluid are altered in mice with genetic deficiencies of the serotonin transporter. How these adaptations influence the sensitivity of these mice to drugs that target these sites (i.e. antidepressants) is a focus of these studies.
Funding Agency	NIH/NIDA
Title	Vulnerability to Opioids: A Mouse Model
Status	Active
Period	9/2008 - 5/2012
Role	Principal Investigator
Grant Detail	The abuse of prescription opioid analgesics by adolescents is on the rise. This is particularly worrisome because little is known about the effects of opioids in adolescents, and because adolescence appears to be an especially vulnerable period during which drugs may have different, longer-lasting effects than during adulthood. The studies in this application use adolescent animal models to learn more about the risk factors for abuse of prescription opioid analgesics, which will help to develop approaches to prevent and treat this important public health issue.
Funding Agency	NIH/NIMH
Title	Increased vulnerability of BDNF deficient mice to mild stress
Status	Complete
Period	5/2009 - 4/2012
Role	Co-Investigator
Grant Detail	Brain-derived neurotrophic factor (BDNF) plays a fundamental role in determining the plasticity and functional architecture of neurons in the adult brain. A frequent, non-conservative polymorphism in the human BDNF gene has been recently identified, which results in impaired secretion of BDNF and may be one factor that increases the susceptibility of an individual to psychiatric disorders brought about by stress, such as major depression. Mice offer a unique opportunity to examine interactions between environmental factors, such as stress, and genetic factors, such as a deficiency in BDNF, in determining behavior. We have interesting preliminary data that indicate that the mild stress of handing and injection of saline, which does not alter behavior in wild-type mice, produces depression-like behavior in male BDNF(+/-) mice. Our overall hypothesis is that BDNF deficient mice are more vulnerable to the effects of mild stress than the wild-type mice. We will use intraperitoneal injection of saline as a mild handling stress. The injection of saline will be used as a temporally discrete and simple stressor to which mice easily habituate. Because BDNF promotes activity-dependent synaptic plasticity, and may have a role in the modulation of responses to repeated stress, we hypothesize that mice deficient in BDNF will not habituate to repeated injections of saline. We will measure plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone as a physiological indication of the reactivity of BDNF(+/-) mice to stress immediately following the acute (3 injections of saline over 24 hours) and chronic (once daily injection of saline for 7 days) handling stress procedures (Specific Aim 1). In this exploratory proposal, rather than attempt to model the complex syndrome of major depression, we will model symptoms of depression that are hallmarks of this disorder such as (a) despair, and (b) loss of interest in normally pleasurable activities or anhedonia. To this end,
Funding Agency	NIH/NIDA
Title	Delay Discounting and fMRI in Rhesus Monkeys
Status	Complete
Period	5/2008 - 4/2011
Role	Co-Investigator
Grant Detail	The goal of this project is to develop a delay discounting procedure in non-human primates that is compatible with brain imaging and can be used to evaluate how neural substrates are affected by drugs of abuse.

Funding Agency	NARSAD
Title	Early life stress, genetic vulnerability, and affective disorders
Status	Complete
Period	9/2006 - 8/2010
Role	Principal Investigator
Grant Detail	The goal of this project is to increase our understanding of the role of individual risk factors in the etiology of affective disorders.

Return to directory listing

Year	Degree	Discipline	Institution
1985	Postdoctoral Fellowship	Pharmacology	University of Michigan Ann Arbor , MI
1984	PhD	Behavioral Pharmacology	University of Utrecht Utrecht , The Netherlands
1978	MS	Physiological Psychology and Statistics	University of Utrecht Utrecht , The Netherlands
1974	BS	Psychology	University of Utrecht Utrecht , The Netherlands

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