While the "crack baby" hysteria of the 80s was greatly exaggerated, researchers say that cocaine use during pregnancy can cause subtle but disabling cognitive impairments in offspring. Vanderbilt researchers, writing in the Journal of Neuroscience, note that cocaine exposure in utero can lead to attention deficits, learning disabilities and emotional problems. Central to the problem, according to Vanderbilt's Gregg Stanwood, is that cocaine causes lasting displacement of dopamine receptors in certain brain cells, which alters their ability to function normally. So far, the effect has only been noted in animal experiments, but the researchers plan to start looking for similar effects in cocaine exposed infants. "The hysteria surrounding the 'crack baby' was sort of overblown," said Stanwood. "In women who have abused relatively low recreational doses of cocaine, it is actually very hard to distinguish those children at birth from children born to anyone else. However, as those children age, they do develop deficits in their cognitive and emotional development."
The study notes that exposed children often exhibit attention and arousal problems, similar to children with attention deficit hyperactivity disorder (ADHD). However, the standard treatments for ADHD - Ritalin and other stimulants - are not always effective in these children.
Several years ago, Stanwood and co-researchers established that exposure to low levels of intravenous cocaine during a very short window of time during gestation - equivalent to the late first trimester and early second trimester in humans - caused specific alterations in brain circuits that use the neurotransmitter dopamine. Additionally, these cocaine-exposed offspring showed attention problems as well as insensitivity to stimulants like amphetamine, suggesting that cocaine exposure had altered the development of the dopamine pathways in the brain. The researchers isolated a particular receptor protein, the dopamine D1 receptor, that is involved in regulating the formation of cortical circuitry. This receptor is also involved in the behavioral effects of amphetamines and cocaine.
"The current study was an attempt to look at the mechanism of this decrease in D1 receptor signaling," explained Stanwood, who examined the levels of D1 receptor in brain cells taken from "teenage" rabbits that were exposed to cocaine during that short, sensitive prenatal period. He found that cocaine exposure did not alter the total amount of D1 receptor produced in the brain. However, there was a dramatic alteration in the location of the protein within the cell. "It's not where it should be," he said. "D1 receptors are normally found at the cell surface, but neurons from the cocaine-exposed animals showed the receptor was predominantly sequestered inside the cells."
"The fascinating thing is that this effect appears permanent," said Stanwood. Implying that cocaine exposure during a brief, sensitive period of neural development can lead to long-lasting effects at the cellular level. What remains to be determined, he explained, is whether D1 receptor localization is affected in humans exposed to cocaine prenatally. "Neither we nor anyone else has yet identified whether this mechanism occurs in the human population," Stanwood said, "so that is a critical next step."
Source: Vanderbilt University Medical Center
