This is a weekend edition of Neury Thursday because I have spent the past week preparing for my departmental seminar which I gave yesterday. And I spent last night embracing the return of Christmas ale season. So, today I review an article from this week’s Journal of Neuroscience, which was one of three addiction-related publications featured in this week’s journal.
And it’s circadian relevant too.
Canadian researchers have shown that the rhythmic expression of PER2, a critical component of the molecular feedback loop that stabilizes endogenous circadian rhythmicity, is driven by rhythms of dopamine release. This was investigated by completely eradicating dopamine expression on one side of the cerebral cortex or administering a dopamine antagonist (specifically for D2 receptors), and comparing changes in PER2 and c-fos expression, a marker of neuronal activity, with the intact cortex. Chronic infusions of a dopamine agonist and the wheel-running induction of dopamine release were also utilized. The two structures of interest were the SCN (duh!!!) where Per2 expression is abundant, per usual, and the striatum which also expresses PER2 and is largely known to influence craving for alcohol.
First, they found that Per2 expression within the SCN and striatum are 12 hrs out-of-phase, meaning that PER2 expression peaks in the striatum near lights-on while those in the SCN peak near light-off. The later result is no surprise because light can also drive PER2 expression. Placing an animal under constant darkness significantly blunts PER2 expression.Presentations of a brief, light pulse at night can also elicit the same response. Secondly, once dopamine was ablated from the brain, PER2 expression within the striatum failed to show a rhythm with levels remaining extremely low across a 24 hr period. There was no effect on PER2 rhythms within the SCN however. The dopamine synthesis blocker also suppressed wheel-running behavior and subsequent dopamine release, reconfirming previous work that exercise is a highly rewarding behavior in rodents…..(potent enough to even suppress alcohol intake….). Similarly, infusions of a dopamine agonist rescued PER2 expression within the striatum.
To satisfy my research narcissism, I wish that the experimental aims were flip-flopped, or perhaps they will be in the near future. That is, how does PER2 expression, either over-expression or under-expression (such as using my own Per2-deficient mice) influences dopamine release in the striatum??? If there is in fact a reciprocal, or even linear, relationship between PER2 expression and dopamine, this would be a great area of advancement within circadian rhythms (perhaps even persuade the NIH not to eradicate the Sleep/Circadian Rhythms Section of the Center of Scientific Review). And of course, provide even more grounding evidence that the circadian timing system and its constituents influence addiction.
Hood S, Cassidy P, Cossette MP, Weigl Y, Verwey M, Robinson B, Stewart J, & Amir S (2010). Endogenous Dopamine Regulates the Rhythm of Expression of the Clock Protein PER2 in the Rat Dorsal Striatum via Daily Activation of D2 Dopamine Receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (42), 14046-58 PMID: 20962226