learning disabilities, investigators discover
Taking cocaine during pregnancy causes possibly permanent changes in an area of the brain that governs short-term memory, leading to symptoms that are very much like attention deficit hyperactivity disorder, Yale researchers have found in two recent studies.
The research team in the Neuropsychopharmacology Laboratory at the School of Medicine found that prenatal exposure to cocaine leads to over-stimulation of the medial prefrontal cortex of the brain in the offspring, and a dramatic impairment in learning.
"Children exposed to cocaine in the womb may have a problem with excitable neurons in the part of the brain that helps control attention and memory," says Bret Morrow, associate research scientist, associate clinical professor and lead author of both studies.
"The use of cocaine among women of childbearing age is alarmingly high," he adds. "When a pregnant woman uses cocaine, she also exposes her fetus to the drug. Studies have shown that these cocaine-exposed children have increased occurrence of symptoms similar to those seen with attention deficit hyperactivity disorder -- increased distractibility, impulsivity and select learning deficits. Based on our animal studies, we are concerned the effects could very well be lifelong in humans."
The first study, published in the February issue of Behavioral Brain Research, involved administering cocaine to pregnant rats and then assessing short-term memory in the offspring when they were adolescents and adults.
The test animals were placed in a cage with two identical objects. They were then removed from the cage for a brief interval, and later put back in with one of the former objects and a second, new object. If the animal explored the new object preferentially, that was taken as evidence that the animal remembered the first object. The test is similar to one used with human subjects.
"Those animals exposed to cocaine prenatally did very poorly on these tests," Morrow says.
The second paper published in the February issue of Neuropsychopharmacology focuses on the theory that the frontal and prefrontal cortex, which are involved in short-term memory, are in some way altered when fetuses are exposed to cocaine.
The researchers examined the brains of animals exposed to cocaine in the womb and found that the medial prefrontal cortex showed dramatic activation not seen in other cortical regions. To do this, they measured the product of a gene, FOS, which is made in an excited neuron and used to activate other genes. These secondary genes can change the way a neuron responds to a stimulus the next time it occurs. "This is thought to be one mechanism by which a neuron 'learns,'" Morrow says, noting that the excess activation may contribute to poor short-term memory.
The studies reveal the long-lasting effects on the circuitry of the brain that occur after exposure to cocaine at a critical stage in development, he says. "Essentially, the brain appears to become re-programmed in a subtle way, causing it to respond abnormally to routine events."
Coauthors on both studies were John Elsworth, senior research scientist in psychiatry and pharmacology, and Robert Roth, professor of psychiatry and pharmacology.
-- By Jacqueline Weaver
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