The drugs increased levels of delta-FosB, a protein associated with addictive behavior, in two brain regions in adolescent mice, researchers concluded. Amphetamine did not increase delta-FosB in the two regions in adult and very young mouse brains and cocaine did not induce an increase in one of the brain areas.
The finding could help in the development of therapies for teen cocaine and amphetamine abuse. It also has implications for the widespread use of amphetamine-like substances in treating attention deficit hyperactivity disorder, or ADHD, researchers said.
The study, conducted at the Nathan Kline Institute in Orangeburg and Temple University in Philadelphia, is the first to analyze these brain changes systematically in response to cocaine and amphetamine at young ages in any species. It will appear in the November issue of the Journal of Neuroscience.
Previous research has suggested that the genes targeted by delta-FosB become more active by the protein and stay more active for extended periods of time, lead author Michelle Ehrlich, a child neurologist at Farber Institute for Neuroscience at Thomas Jefferson University in Philadelphia, told United Press International.
"The challenge now is to identify the key target genes, particularly in the adolescent brain," she said. "Another possibility is that among the genes that are upregulated (more active) are a group of genes that are structural genes, which ultimately change the structure of the connections, or the synapses between the (brain) cells," Ehrlich said.
The researchers gave injections of cocaine, amphetamine or salt water to very young, adolescent and adult mice for seven days. They then examined the animals' brains for accumulations of delta-FosB in two regions. After amphetamine and cocaine dosing, the nucleus accumbens, a region in the brain strongly associated with addictive mechanisms and reward, showed increased levels of delta-FosB in the adolescent mice but not the very young or the adult mice.
Amphetamine also caused increased levels of delta-FosB in the caudate putamen, a region associated with movement and with movement disorders that also is highly implicated in attention deficit hyperactivity disorder.
"I think this is important work because it suggests that there are patterns of gene expression that may predispose to drug addiction at various points in the developmental span," Joe Miller, neuropharmacologist at University of Southern California in Los Angeles, told UPI.
However, the mouse study results cannot be applied directly to human adolescents and the research could be improved by looking at animals at more than three developmental stages points, Miller added.
"The frustrating thing with identifying increased activity of a (protein) such as delta-FosB is that it's only a first step. We know it simulates other genes, but after that it is not at all clear what changes result from this," Miller said.
"The challenge will be to learn what is the consequence of these changes in gene expression and which of these downstream effects are critical targets for reversal of the negative aspects of addiction," James A. Bibb, assistant professor of psychiatry at University of Texas Southwestern Medical Center in Dallas, told UPI.
Delta-FosB could promote long-lasting changes in the nerve connections in the brain, according to Bibb, who is researching the issue. Cocaine and amphetamine produce their immediate effects by changing the way nerves communicate with one another.
(Reported by Joe Grossman, UPI Science News, in Santa Cruz, Calif.)
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