Everyone seems to know that smoking is bad for you. If lung cancer doesn’t scare the crap out of you, emphysema certainly will. And most people now know that it would be better for their health if they quit. Unfortunately, quitting is EXTREMELY hard to do. Nicotine is an incredibly addictive drug, and it, and the behaviors associated with smoking, can be a Herculean habit to kick. By far the best possible thing to do is never to have started at all.
But that’s not so easy either. Most smokers who are smokers as adults started when they were teenagers. And teenagers are a very different neurological animal (some adults would call them scary, I call them misunderstood. I’m sure they would agree). During adolescence, the brain undergoes MASSIVE pruning of connections, with some neurons dying while others form new friends and wire the brain for adulthood. These changes are accompanied by behavioral changes (and I’m not talking a new found interest in girls). Adolescents are FAR more impulsive than adults, and exhibit increased risk-taking behavior, where they weight the potential benefits of something risky far more heavily than the potential consequences. And so getting adolescents to stop from smoking that first cigarette can be a daunting task. And of course many adolescents are ALREADY smoking, and it’s now a matter of getting them to quit.
So while some efforts focus on getting adolescent smokers to quit and to prevent them from beginning in the first place, others are interested in what happens in those who smoke while they are teenagers. People who begin smoking as teenagers show attentional decreases and problems with working memory, and in adulthood will show increased behavioral problems and mental health disturbance. But how much is this from the SMOKING? Does smoking CAUSE behavioral problems? Or are people with behavioral problems just more likely to smoke? After all, people with mental disorders are known to self-medicate with drugs such as nicotine (90{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of people with schizophrenia smoke, for example). So we know there’s a correlation between smoking and behavioral problems in adulthood, but we don’t know whether it is causation. Looking in humans isn’t going to help you here.
Which is why we need RATS. Rats doing attentional tasks. And smoking…
(Source)
Ok, not really.
Counotte, et al. “Lasting synaptic changes underlie attention deficits caused by
nicotine exposure during adolescence.” Nature Neuroscience, 2011.
First off, the animals were treated with nicotine (or not) as teenagers. When they reached adulthood, they were trained on a 5 choice serial reaction time task. This is a task where the rat has a choice between five holes. When the test starts, a hole is lit. If the rat nosepokes in the lit hole, he gets a treat. If he screws up and either doesn’t nosepoke or nosepokes somewhere else, no treat for you. Not only that, if the rat responds with nosepokes when NO hole is illuminated, he also gets no treat. Rats get pretty good at this, and you can use the issues they have with it as a measure of things like impulsivity and attention. For example, if a rat nosepokes and there’s never been a light, that’s a measure of impulsivity, moving without a cue. While if the fails to look for the light cue and is doing something else and doesn’t respond, its taken as a measure of attentional deficit.
You can see here that the rats treated with nicotine as teenagers showed both decreased accuracy (bad attention) and higher impulsivity as measured by the premature choices. But the rats treated with nicotine as adults showed no differences, which suggests that the nicotine treatment affects adolescents in this way specifically. But the question now is: what are the changes in the brain that underlie this?
The scientists looked at the protein levels in the synapses of the prefrontal cortex, to see what had changed in adult rats when they were exposed to nicotine as teenagers. They found that one specific protein, mGluR2 (which stands for metabotropic glutamate receptor 2) was changed as a result of ONLY teenage nicotine exposure (adult nicotine exposure had different effects). mGluR2 is a big deal for many reasons, but the biggest is that it is a receptor for the main excitatory neurotransmitter in the brain: glutamate.Activation of mGluR2 in adolescents suppresses glutamate transmission.
In this case, adolescents treated with nicotine so adolescents exposed to nicotine showed a decreased response to glutamate in adulthood, which correlated with their decrease mGluR2 receptors, suggesting that the lack of mGluR2 receptors was contributing to a decreased glutamate response, and that this was contributing to the behavioral problems seen in the 5 choice task.
But WAS it the mGluR2? It looks like it. Giving the nicotine treated rats a mGluR2 AGONIST to stimulate the subsensitive receptors reversed the attentional problems the rats had. You can see below that when you give the rats an mGluR2 agonist, their accuracy increases. But what’s cool is that their premature responses do NOT change. This means that the mGluR2 effects may be limited to the attentional problems, while the problems the nicotine treated rats have with impulsivity may be due to other changes.
They also used an mGluR2 ANTAGONIST in normal rats, and found that it decreased their attention spans (I think, anyway, the data was in the supplement and I couldn’t find anything very clear there).
This study has a couple of different implications. First, it shows one of the ways that adolescent nicotine exposure can change your behavior in adulthood, and shows the neural mechanisms that underlie it. But it also makes me (and probably the authors) think hard about what mechanisms may underlie problems with attention deficits. Right now, we treat disorders like ADHD with dopaminergic drugs. There are studies showing that glutamate may be a factor in ADHD, and it would be interesting to see if people with ADHD have changes in glutamate receptors like those seen in this study, and if that could uncover new ways to treat attention deficits.
As a side note: The data in this paper is good. But please, scientists, we can write better than this. EXPLAIN your procedures clearly, as well as what the changes you found WERE. The phrase “is altered” tells me pretty much nothing. In addition, journal editors, if I have to go to your supplemental data to find out HOW and for how long they treated their rats…something’s up. And when the supplemental data has its OWN results and discussion, something is REALLY up. All because Nature Neuroscience accepts only the best…at a 3 page limit. Nature Neuroscience? This is RIDIC. We’re all accessing this on the web, the least you can do is combine it all in a single pdf for download. Justsayin’.
Counotte DS, Goriounova NA, Li KW, Loos M, van der Schors RC, Schetters D, Schoffelmeer AN, Smit AB, Mansvelder HD, Pattij T, & Spijker S (2011). Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nature neuroscience, 14 (4), 417-9 PMID: 21336271
