The runner’s euphoria and opioids

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The runner’s high is most likely due to release of the endorphins binding to the opioid receptors according to Boecker et al. (2008, doi: 10.1093/cercor/bhn013). Image courtesy of Pixabay.

We all know that exercise is good for you: it keeps you fit, it reduces stress and improves your mood. And also, sometimes, particularly after endurance running, it gets you high. The mechanism of euphoria reported by some runners after resistance training is unknown. Here is a nice paper trying to figure it out.

Boecker et al. (2008) scanned 10 trained male athletes at rest and after 2 hour worth of endurance running. By “trained athletes” they mean people that ran for 4-10 hours weekly for the past 2 years. The scanning was done using a positron emission tomograph (PET). The PET looks for a particular chemical that has been injected into the bloodstream of the subjects, in this case non-selective opioidergic ligand (it binds to all opioid receptors in the brain; morphine, for example, binds only to a subclass of the opioid receptors).

The rationale is as follows: if we see an increase in ligand binding, then the receptors were free, unoccupied, showing a reduction in the endogenous neurotransmitter, that is the substance that the brain produces for those receptors; if we see a decrease in the ligand binding it was because the receptors were occupied, meaning that there was an increase in the production of the endogenous neurotransmitter. The endogenous neurotransmitters for the opioid receptors are the endorphins (don’t confuse them with epinephrine a.k.a. adrenaline; different systems entirely).

After running, the subjects reported that they are euphoric and happy, but no change in other feelings (confusion, anger, sadness, fear etc.; there was a reduction in fear, but it was not significant). The scanning showed that it was less binding of the opioidergic ligand in many places in the brain (for the specialist, here you go: prefrontal/orbitofrontal cortices, dorsolateral prefrontal cortex, anterior and posterior cingulate cortex, insula and parahippocampal gyrus, sensorimotor/parietal regions, cerebellum and basal ganglia).

Regression analysis showed that there was a link between the euphoria feeling and the receptor occupancy: the more euphoric the people said they were, the more endorphines (i.e. endogenous opioids) they had bound in the brain. This study is the first to show this kind of link.

Reference: Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, & Tolle TR. (Nov 2008, Epub 21 Feb 2008). The Runner’s High: Opioidergic Mechanisms in the Human Brain. Cerebral Cortex, 18:2523–2531. doi:10.1093/cercor/bhn013. Article | FREE FULLTEXT PDF

By Neuronicus, 28 November 2015

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Giving up? Your parvalbumin neurons may have something to do with it

Cartoon from http://i393.photobucket.com/albums/pp20/saisi24/dontgivedup.jpg, licensing unknown
Cartoon from Photobucket, licensing unknown.

One of the most ecologically-valid rodent models of depression is the learned helplessness paradigm. You get a rat or a mouse and you confine it in a cage with an electrified grid. Then you apply mild foot shocks at random intervals and of random duration for an hour (which is one session). The mouse initially tries to escape, but there is no escape; the whole floor is electrified. After a couple of sessions, the mouse doesn’t try to escape anymore; it gives up. Even when you put the mouse in a cage with an open door, so it can flee to no-pain freedom, it doesn’t attempt to do so. The interpretation is that the mouse has learned that it cannot control the environment, no matter what he does, he’s helpless, so why bother? Hence the name of the behavioral paradigm: learned helplessness.

All antidepressants on the market have been tested at one point or another against this paradigm; if the drug got the mouse to try to escape more, then the drug passed the test.

Just like in the higher vertebrate realm, there are a few animals who keep trying to escape longer than the others, before they too finally give up; we call these resilient.

Perova, Delevich, & Li (2015) looked at a type of neuron that may have something to do with the capacity of some of the mice to be resilient; the parvalbumin interneurons (PAI) from the medial prefrontal cortex (mPFC). These neurons produce GABA, the major inhibitory neurotransmitter in the brain, and modulates the activity of the nearby neurons. Thanks to the ability to genetically engineer mice to have a certain kind of cell fluoresce, the researchers were able to identify and subsequently record from and manipulate the function of the PAIs. These PAIs’ response to stimulation was weaker in helpless animals compared to resilient or controls. Also, inactivation of the PAI via a designer virus promotes helplessness.

Reference: Perova Z, Delevich K, & Li B (18 Feb 2015). Depression of Excitatory Synapses onto Parvalbumin Interneurons in the Medial Prefrontal Cortex in Susceptibility to Stress. The Journal of Neuroscience, 35(7):3201–3206. doi: 10.1523/JNEUROSCI.2670-14.2015. Article | FREE FULLTEXT PDF

By Neuronicus, 21 October 2015