Anyone who has taken Adderall or Ritalin to have “tunnel vision” during finals week knows about the unfortunate side effect: the 48 hr period of a racing heart, no sleeping, and the constant urge to move around. But this isn’t nearly as counterintuitive to the fact that those who are clinically diagnosed with ADHD are calmed by ADHD medication. This phenomenon and its neurobiological mechanisms were presented in this week’s Journal of Neuroscience. I applaud the authors of this study for using such a vast and comprehensive repertoire of advanced neuroscience techniques to address the ADHD paradox: including three different types of behavioral testing (adjustment to novel environments, object recognition (familiar vs. unfamiliar), and hyperactivity) , electrophysiology to characterize neuronal activity, Western blotting to quantity protein phosphorylation, and HPLC to assess dopamine kinetics. Using an array of psychostimulants that affect dopamine kinetics, such as cocaine, methamphetamine, haloperidol, and others I typically don’t remember, the researchers gave wild-type and ADHD-like mice a drug challenge and subsequently undertook all of the behavioral, physiological, and molecular experimentation described above. I should mention that the ADHD mouse model lacked dopamine transporter uptake, causing high levels of dopamine to be retained in the synapse and elicit hyperactivity. This was behaviorally and physiologically confirmed throughout the experiments as shown here.
What were the results? As anticipated, the ADHD-like mice showed reduced responsiveness to the psychostimulants as shown here. The opposite was true for wild-types. The drugs also increased protein phosphorylation, which is one of the underlying mediators of the ADHD paradox.
Aside from the observation that this research re-confirms the widely known ADHD paradox, it is a great example of a basic neuroscience principle; what happens when you have too much of a neurotransmitter. In this case, the dopamine systems compensate for dopamine overexpression in the synapse by downregulating receptors and molecular machinery, so when a response is finally elicited by dopamine binding to its receptor, it’s less dramatic. Recently, I’ve also read an article stating that ADHD meds are an effective hedonic substitute for alcoholism. Taking it makes alcohol dependent mice drink less. Though, obviously, while this is interesting, ADHD medications as a hedonic substitute in alcoholics is certainly not the resolution; “treating” one addiction by encouraging another. Exercise is a healthy hedonic substitute though.
Most importantly, this research article should be posted in many pediatric offices around the US because as you may know, America has a problem with of over-diagnosing ADHD. Kids can’t be kids anymore. Perhaps a slip of ADHD medications is the answer to making an accurate and unbiased diagnosis of ADHD, but of course, there’s plenty of ethical issues with that. But is this the only way?
Francesco Napolitano,1* Alessandra Bonito-Oliva,1* Mauro Federici,2* Manolo Carta,3 Francesco Errico,1, Salvatore Magara,1 Giuseppina Martella,4 Robert Nistico`,2,5 Diego Centonze,2,4 Antonio Pisani,2,4 Howard H. Gu,6, & Nicola B. Mercuri,2,4 and Alessandro Usiello1,7 (2010). Role of Aberrant Striatal DopamineD1 Receptor/cAMP/Protein
Kinase A/DARPP32 Signaling in the Paradoxical Calming Effect
of Amphetamine Journal of Neuroscience, 30 (33), 11043-11056 : 10.1523/JNEUROSCI.1682-10.2010
2 Comments until now
Your final paragraph fell a bit flat here…I’m not really sure how what you say follows from the preceding text… Would you please elaborate? Further, what is the relationship between exercise & ADHD treatment…by evoking exercise, are you suggesting that exercise can serve as an hedonic substitute for ADHD meds?
I could blame myself for the lack of clarity and elaboration, but I would like to blame montegraphia more. At the time I was writing this entry, it was 1030 at night and he was nagging me “geez! turn off your computer, go to sleep! geez!” But yes, there is a tremendous amount of literature now (even work THE HAMMER and I did), showing that any type of reward, either drug or natural, can serve as a hedonic substitute for another. Hedonic substitute referring to the fact that the substituted reward can elicit the same intensity of dopamine release within the CNS, and hence, satisfy the brain’s wanting for rewards. Whether it’s exercise, amphetamines, or even cocaine (which I’ve seen in the literature too), all of these have been used specifically to suppress alcohol consumption and vice versa. Hope this helps!!!
Add your Comment!
You must be logged in to post a comment.