Adolescents are highly at risk for abusing drugs. Now, Yale researchers may have a better understanding as to why.
A new study published this week in the journal of the Proceedings of the National Academies of Science builds on previous research which claimed that cocaine changes the shape of brain cells. Postdoctoral fellow Shannon Gourley and her team, however, took this one step further by investigating whether this change in the structure of neurons had any effect on behavior. They discovered that learning ability and sensitivity to cocaine may indeed determined by the shape of brain cells, and this, mental health workers say, could explain why adolescents have such a hard time dealing with drugs.
“One of the things we’ve known is that psycho-stimulants like amphetamine, which is a key component in Ritalin and cocaine, can change shape of brain cells,” Gourley said. “What we’ve done in this study is turned that question on its head.”
The research project came about as a result of Gourley’s and fellow author Anthony Koleske’s common interest in the connectivity of neurons. Koleske’s previous research concerns the stabilization of connections between neurons, and Gourley had insight into how this knowledge might be relevant to issues involving the pre-frontal cortex of the brain, said Koleske, who is an associate professor of molecular biophysics and biochemistry and of neurobiology.
Cell shape is critically important to the ability of neurons to communicate with each other, Gourley said.
“A cell is like a tree,” she said. “If it’s really big and complex, it is very likely to touch other trees in the forest. If it is damaged, or has only a few branches, then there will be fewer points of contact.”
Neurons in the frontal cortex of the brain, which controls higher-order mental functions, do not stabilize until late adolescence in part due to a gene called Arg, which is key to adolescent development. In this study, Koleske created “knock-out” mice in which Arg was disabled. As a result, the mice had unstable neurons even as adults.
At this point, the mice were given either cocaine or salt water. Gourley said mice who had been given cocaine, a stimulant, ran around a lot more. Interestingly, the “knock-out” mice were a lot more active, even when given amounts of cocaine so small that the normal mice were not affected — underscoring that immature brain cells heightens one’s sensitivity to drugs like cocaine.
The second part of the experiment looked at the behavioral flexibility of the mice after exposure to cocaine.
“Behavioral flexibility is the ability to change one’s behavior,” Gourley said. “For instance, if you grew up and lived in one house for 15 years and then moved, you’d need to be able to drive to your new house.”
The researchers found cocaine severely affected the “knock-out” mice’s ability to learn new things, even after the cocaine had left the animals’ systems.
Mary Torregrossa , a postdoctoral fellow at the Connecticut Mental Health Center, said this new study provides the first evidence of a neurobiological mechanism that explains why adolescents might be more sensitive to the effects of drug abuse than adults.
“The research suggests that it is of particular importance to educate adolescents about the dangers of drug use, as they may be especially vulnerable,” she said.
Torregrossa also added that some individuals might have certain genetic predispositions or environmental experiences that affect cortical development. This, she said, leaves the individual susceptible to develop addictions. If these factors were identified, treatments could be developed to specifically target these individuals.
Gourley said that the next step is to find out what part of the changing neuron causes the increased sensitivity to drugs like cocaine.
“What we want to know is, which receptor that we are losing is really important?” Gourley said. “And if we could rescue these receptors, could we reverse the effects?”
The study was funded by the National Institutes of Health and the Connecticut Department of Mental Health and Addiction Services.