The research team in the Neuropsychopharmacology Laboratory at Yale School of Medicine found that prenatal exposure to cocaine leads to over-stimulation of the medical 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 part of the brain that helps control attention and memory," said Bret Morrow, associate research scientist, associate clinical professor and lead author of both studies. "Potentially, this excitable prefrontal cortex may be the basis of the learning deficits in these children."
"The use of cocaine among women of childbearing age is alarmingly high," he added. "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 then 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 said.
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. The product of a gene, FOS, was used to measure this activation. Fos, a protein, is made in an excited neuron and then it is used to turn on 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 said. "We believe that the excess activation in the prefrontal cortex plays an important role in the poor short term memory in these."
He said the studies were another step toward understanding and treating the long-lasting effects on the circuitry of the brain that occurs after exposure to cocaine at a critical stage in development.
"Essentially, the brain appears to become re-programmed in a subtle way, causing it to respond abnormally to routine events," Morrow said.
Co-authors on both studies were John Elsworth, senior research scientist in psychiatry and pharmacology, and Robert Roth, professor of psychiatry and pharmacology.