Are the estimated 1 million young adults who were exposed to cocaine before birth more vulnerable to drug abuse today? New research indicating long-lasting brain changes suggests the possibility -- especially in males -- according to a report from Wake Forest University School of Medicine.
At the annual meeting of the American Society of Pharmacology and Experimental Therapeutics in San Diego, Calif., April 7, the scientists reported that adult male monkeys that were exposed to cocaine in the womb appear to have altered function of an important target in the brain, known as dopamine 3 (D3) receptors. In humans, altered dopamine receptor function is associated with increased vulnerability to drug abuse.
"This was a unique opportunity to study the possible long-term effects of fetal cocaine exposure," said Lindsey R. Hamilton, a graduate student in the laboratory of Michael Nader, Ph.D., a professor of physiology and pharmacology. "These animals were exposed to cocaine in the womb 13 years ago and have had little experience with drugs since."
There are five known receptors for dopamine, a chemical in the brain that is similar to adrenaline. Dopamine affects brain processes that control movement, emotional response, and ability to experience pleasure and pain. Drugs such as cocaine and heroin target this reward system by increasing levels of dopamine.
The scientists looked for differences in the dopamine systems of animals that had prenatal exposure to cocaine versus those that had no exposure. Studying D1 and D3 receptor levels was simple -- there are drugs that stimulate the receptors and induce easily observable behaviors such as eye blinking (D1) or yawning (D3.)
The researchers saw no differences in the D1 system in the two groups of animals. But, the male monkeys who had been exposed to cocaine yawned almost twice as much during a 30-minute period as males who had no drug exposure.
"This was particularly striking considering that the prenatal exposure was more than 13 years ago," said Hamilton. "It suggests that these animals have either an increased number of D3 receptors or that the receptors have higher function or sensitivity."
Human autopsy studies show higher numbers of D3 receptors in those who have died from cocaine overdose.
To look for differences in D2 receptors, the researchers used positron emission tomography imaging. They found no difference between the two groups of animals. In humans, lower levels of D2 receptors are associated with increased vulnerability to drug abuse.
Next, the researchers will conduct studies in which the animals can self-administer cocaine to determine whether the males exposed to cocaine in the womb will be more vulnerable to abuse than the other animals.
"Just because there is a difference in the D3 system doesn't mean it will increase their vulnerability to cocaine use," said Hamilton. "Further research will help us answer the question raised by our preliminary research -- whether male children who are exposed to cocaine in the womb may be more vulnerable. It's a timely question both because many who were exposed prenatally are now young adults and because cocaine abuse amongst young women of childbearing age is a growing problem in this country."
The research was funded by the National Institute on Drug Abuse and was part of Wake Forest's Center for the Neurobiological Investigation of Drug Abuse. Co-researchers were H. Donald Gage, Ph.D., in the Department of Radiology, and Tonya L. Calhoun and Michael A. Nader, both in the Department of Physiology and Pharmacology.
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