Journal Club: No Smoking Allowed

We haven’t done a journal club in a while, so I figured I couldn’t resist delving into the science behind another one of those scientific newspaper articles that love tohype it up. It all started with one of those articles that people share on Facebook, the title of which translates to:

“Peptidediscovered to stop smoking definitively and without relapse!” Wow, that’s some discovery! This article linked me to a statement released from the Center for Addiction and Mental Health, which of course actually had a far more toned down title: “CAMH discovery may lead to new treatment to prevent smoking relapse”. O.K., we’re digging down past the layers of hype.

Of course both of these articles committed my worst pet peeve ever: they didn’t cite the actual article, and it took me forever to find it. It’s not on Science Direct or Google Scholar yet, PubMed only has the abstract, I finally managed to find it on the webiste of the Journal of Experimental Biology, also because the actual title they landed on was:

“The α7nACh–NMDA receptor complex isinvolved in cue-induced reinstatement of nicotine seeking”

Yeesh, good thing they accompanied this article with a press release, cause that’s a pretty specific and boring title that would not have led me to open that article and read on, nor does it make it easy to find in a search engine. Anyway, this is the part where I read the actual article and digest it into easier morsels for you, like a mother bird barfing up her dinner. So let’s see, what did they actually conclusively find?

Let’s start with what we know: we know that there are receptors in our brains called nicotine acetylcholine receptors, or nAChRs. These receptors are activated by nicotine, which in turn cause the yummy feelings in our brains, which is what makes smoking additive and hard to give up, especially over long periods of time (don’t I know it). What remains fuzzy is exactly what these receptors do on a molecular level after they receive the nicotine fix, therefore the molecular source of what exactly makes smoking so hard to give up.

Here, they found that one particular receptor of the nAChR family, called α7nAChR, forms a complex with another kind of receptor called NMDAR, under chronic exposure to nicotine. This means that the formation of this complex could be a key component to understanding what makes it hard to quit. Therefore, theoretically, if you stop this complex from forming, you could prevent the downstream warm-and-fuzzy effects on the brain that this complex induces, and thus making it easier to give up the cigs. With me so far?

In order to test this hypothesis, the researchers got rats addicted to nicotine, teaching them that if they pressed down on a lever, they got a shot of nicotine. Once they were well addicted and their self-administration of nicotine became relatively stable, they were given a shot of a peptide that the researchers showed interferes with the formation of this complex. After this shot, the rats no longer looked to self-administer nicotine. They also made sure that this was not because the peptide simply made the rats loopy, therefore making them less likely to press down on the nicotine bar for different reasons, but they demonstrated that the rats injected with the peptide moved around just as much as normal rats.

This sounds quite promising, so what are the ups and the downs?

One big problem I have with this paper is the lack of focus on the aspect that they focused on in their press release. I understand that the molecular part of the paper is extremely labor-intensive and important, the fact that they conclusively demonstrated the protein complex formation (which is not easy) and found a peptide that inhibits it is a paper all on its own. However, rightly so, they knew that the part of this experiment that would get the most attention is the part about actually testing this peptide to see if it works. However, despite being the only focus of the press release, they completely gloss over it in the paper. There is not a single graph, not a single statistical analysis of the behaviour of the rats.

ICV injection of 12 or 40 nmol TAT- α 7pep2[L336-M345] blocked reinstatement of nicotine seeking, they say. OK, completely? Significantly? That’s it, that’s all the information I get?

TAT- α 7pep2[L336-M345] peptide did not affect locomotor activity (not depicted) why is it not depicted? Did you not run a statistical analysis to demonstrate that the locomotor activity was not affected? If you did, let’s see it! If you’re not going to pay any attention to the behavioural aspect of the experiment then just don’t do it, and you definitely don’t get to make it the sole focus of your press release.

Putting aside my wariness about the nicotine-seeking results of the rats, it is a promising experiment and certainly the first of its kind. Of course there is a very long way to go in applying it to humans: seeing if this complex also forms in humans (tough to do, since in this case they demonstrated it by taking neurons from the rats), and definitely doing a very in-depth analysis of this peptide to make sure that it doesn’t interfere with anything else in the body which is important.

It is a good start, but I still give them a tut tut for their handling of some of the data.