In a new study, young rats who were given regular, high doses of amphetamine experienced long-term changes in dopamine signaling that persisted into adulthood. Dopamine is a neurotransmitter that plays a central role in memory, attention, learning, and feelings of pleasure.
“The dopamine system, which continues to develop throughout adolescence and young adulthood, is a primary target of psychostimulant drugs like amphetamine,” said lead researcher Joshua Gulley, a psychology professor at the University of Illinois.
“Changes in dopamine function in response to repeated drug exposure are likely to contribute to the behavioral consequences — addiction and relapse, for example — that abusers experience.”
The researchers note that rats are a good model to study human drug addiction — which often begins in adolescence — because of the strong parallels in development among rats and humans.
“[Adolescent] rats exhibit many of the characteristics that human adolescents do. They tend to be more impulsive than adult rats; they tend to make more risky decisions,” he said. They also can engage in “addiction-like behaviors,” he added.
“They show increased drug use in response to stress,” Gulley said. “And, just as in humans, there is evidence that animals that start using drugs in adolescence are more likely to relapse than animals that start in adulthood.”
One limitation of the new study was that while humans generally choose whether or not to partake in drug use, “the rats had no say in whether they got amphetamine,” Gulley said.
Other research conducted by Gulley and his team evaluated the effects of amphetamine abuse on working memory — the ability to hold information in the mind just long enough to use it — in both young and adult rats.
“In that study, we found that animals that were exposed to the drug during adolescence had much more significant deficits in working memory than those exposed during adulthood,” Gulley said.
The researchers hypothesized that drug exposure during adolescence, a time of great changes in the brain, “somehow influences the normal developmental trajectory,” Gulley said. “But how?”
In an effort to figure this out, the researchers focused on the prefrontal cortex, a brain region behind the forehead that is among the last to fully develop during adolescence. The findings show that repeated exposure to amphetamine — beginning in adulthood or in adolescence — reduced the ability of key cells in the rats’ prefrontal cortex to respond to dopamine. In this part of the brain, dopamine essentially tells the cells to stop responding to a stimulus, Gulley said.
“Inhibition in the nervous system is just as important as activation,” he said. “You need cells that are firing and communicating with one another, but you also need cells to stop communicating with one another at certain times and become quiet.
“Our research suggests that a subtype of dopamine receptor, the D1 receptor, is altered following amphetamine exposure,” Gulley said. “It’s either not responding to dopamine or there are not as many of these receptors after exposure as there used to be.”
This change in dopamine signaling remained the same for 14 weeks after exposure to amphetamine in the adolescent rats, he said.
“That’s akin to a change in humans that persists from adolescence until sometime in their 30s, long after drug use stopped,” he said. “Along with other studies, this shows pretty clear evidence that drug use during adolescence, a time when the brain is still developing, has extremely long-lasting consequences that go far beyond the last drug exposure.”
The findings are published in the journal Neuroscience.