Mar 1, 2016 By Stephanie Kossman
How do drugs affect the developing teenage brain? This question has baffled scientists for decades, but one fact remains true — teens are more susceptible to addiction. Scientists have often explained it in the context of social circumstances, such as peer pressure, or the fact that parents who smoke are more likely to raise teen smokers. But two new papers, published together in eLife, argue the reason is far more biological.
Scientists have previously used biology to explain teen alcohol addiction, but it hasn’t been used as a frequent excuse for illegal drug use. “In humans, adolescence, namely the period between the early teenage years and early twenties, is a time of heightened susceptibility to the effects of addictive drugs, but previous studies have struggled to explain why,” said senior author Mauro Cosa-Mattioli, in a press release. “Our studies support the idea that regulation of protein synthesis by eIF2 might be the underlying cause.”
Two separate studies assessed the role of elF2 α, a molecule that regulates the production of proteins responsible for building connections between neurons. In one study, adolescent and adult mice were injected with either a saline solution or a low dose of cocaine. Researchers found only the adolescent mice that were given cocaine experienced a reduction of eIF2α activity, which resulted in changes in protein regulation that strengthened connections between dopamine-storing neurons.
“This greater communication between dopamine-rich neurons gives a greater sense of pleasure from taking the drug and encourages behaviors related to addiction,” said lead author Wei Huang. “Only higher doses of cocaine led to similar responses in adult mice, proving that adolescents have a lower threshold for the effects of cocaine on these neurons.”
The researchers were further able to confirm their results by altering the production of the proteins controlled by eIF2α in adult and adolescent mice, effectively making adult mice appear biologically adolescent and adolescent mice biologically adult. In doing so, the researchers witnessed the converse results from the earlier part of the study. Adolescent mice, now with adult protein structures, showed no change in elF2 α activity and an increased resistance to cocaine. Adult mice, in turn, became more sensitive.
“It’s truly remarkable that by manipulating the processes surrounding eIF2α in this way, we can rejuvenate brain activity. This could hold significant promise for developing new treatments for drug addiction and related disorders,” Costa-Mattioli said.
The second study covered in the paper described similar experiments, albeit with nicotine instead of cocaine. Again, researchers observed the same effects. Using functional magnetic resonance imaging, the study also identified a variation in the human gene that codes for eIF2α. This variation, they found, can either increase or decrease nicotine users’ responses to rewards.
“Our findings are clinically relevant as they identify a novel addiction target in rodents, along with parallel supporting evidence from brain imaging studies in human addicts,” said lead author Andon Placzek.”Our new insights could help educate adolescents about the risks of recreational drug use and experimentation, discouraging these behaviors as a result. They could also help discover a new way to fight addiction in both adolescents and adults, for example by altering the activity of eIF2α in the brain.”
Source: Huang W, et al. Translational control by elF2 α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine. eLife. 2016; Placzek A, et al. Translational control of nicotine-evoked synaptic potentiation in mice and neuronal responses in human smokers by elF2 α . eLife. 2016.