Worldwide, an estimated 25 to 33 percent of people who give themselves a short-acting opiate drug — usually heroin — will
develop an addiction to it. This suggests that some people are naturally more vulnerable to addiction and that genetics may play a role along with environmental and psychological factors. Dr. Kreek focuses on determining how genetics as well as other neurobiological alterations factor into addictive diseases such as opiate addiction, cocaine dependency, nicotine addiction and alcoholism.
Dr. Kreek is interested in determining the biological basis of addictive diseases and in existing and novel treatments for these conditions. Her lab also works to better understand the medical complications of drug abuse, such as hepatitis C and AIDS. Her laboratory in 1983–1984 discovered that the second most common risk group for HIV-1/AIDS are parenteral drug users. Dr. Kreek’s research, both clinical and experimental, focuses on the endogenous opioid system, which the brain uses to manage pain and stress, and on determining the roles of specific opioid peptides and their receptors in both normal and abnormal circumstances.
The opioid family of receptor proteins is widely expressed throughout the body, but especially in the brain and the gut. The receptors are activated by opiates, such as heroin and morphine, because they mimic the action of the endogenous peptides within the body, as well as by cocaine and alcohol. Dr. Kreek’s lab investigates both the physiological and behavioral effects of natural opiate peptides in rats, mice and guinea pigs. Her research compares how these proteins function under normal conditions with animals given chronic or acute doses of a drug of abuse or potential treatment agent. They study the effects of cocaine, opioids and alcohol on the endogenous opioid system and other related signaling networks after acute exposure and how chronic drug exposure can impact or alter the brain’s circuitry due to the intrinsic neuroplasticity of the brain.
To do this, Dr. Kreek’s lab measures the gene expression of opioid receptors, opioid peptides and related proteins, transporters and receptors in specific brain regions, and in specific endocrine and gastrointestinal regions. Using microarray technology, the lab conducts gene expression studies in animal models and human tissue, looking to identify different genetic polymorphisms, which are naturally occurring variations in genetic sequences between individuals. Dr. Kreek’s lab also uses microdialysis in rats and mice to conduct dynamic studies of neurotransmitter release and peptide processing in specific brain regions.
Clinical studies look at neuroendocrine-neurotransmitter function, and the effects of selected neuropeptides in cocaine and heroin addicts, former addicts in methadone maintenance or other treatments, alcoholics and nicotine-dependent patients, with the goal of identifying specific components of the neurobiology of addictive disorders. Her lab examines these patients for polymorphisms both in and outside of the coding regions of genes that may play a role in addiction. Family studies and examinations of different populations are in progress to determine different variations of genes that may have a greater association with addictive disorders.
Dr. Kreek is well known for her work in pioneering methadone maintenance for heroin addiction in the 1960s, a therapy that has become common practice in many parts of the United States and several other countries. Her recent work has led to the identification of a functional single-nucleotide polymorphism in the ì-opioid receptor that may impart a greater likelihood of developing an addiction to a person exposed to opioids. She also was one of the first to document that drugs of abuse significantly alter expression of specific genes, in specific brain regions, alter normal functions and lead to perceptions of “reward” and “dysphoria.”
CAREER
Dr. Kreek received her B.A. from Wellesley
College in 1958 and her M.D. from Columbia
University College of Physicians and Surgeons
in 1962. She (and also Marie Nyswander)
joined Rockefeller University in the laboratory
of Vincent Dole in 1964.
Dr. Kreek was awarded the Gold Medal
for Distinguished Achievements in Academic
Medicine by the Columbia University College
of Physicians and Surgeons Alumni Association
in 2004. In 2000, Dr. Kreek was conferred
with the doctor honoris causa by the University
of Uppsala, Sweden. In 1999, she received the
Nathan B. Eddy Memorial Award for Lifetime
Excellence in Drug Abuse Research and the R.
Brinkley Smithers Distinguished Scientist Award.
She received a Specific Recognition Award for
Research in the Science of Addiction from the
Executive Office of the President in 1998, and in
1996 she was given the Betty Ford Award.
