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Back off, stranger, that’s my mate! The role of kappa opioid receptors

The views expressed are those of the author and are not necessarily those of Scientific American.


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We’ve all heard of the legendary monogamous prairie vole, haven’t we? Our adorable rodent friend forms the kind of attachments that make us humans feel slightly ashamed of our more promiscuous habits. And of course, if we know about prairie voles, we know about oxytocin (and I’ve got a whole series on it over at the ‘Science! 101′ page of my other site). Prairie voles are monogamous primarily due to the actions of oxytocin in the female, and vasopressin in the male. Without these two hormones, the prairie voles will love ‘em and leave ‘em just like their close cousins, the meadow vole.

But is that all there really is to pair bonding? Just one hormone, a desire to stay with your furry mate forever…and that’s it?

No, it’s more complicated than that.

Resendez et al. “K-Opioid Receptors within the Nucleus Accumbens Shell Mediate Pair Bond Maintenance” J. Neuroscience, 2012.


(Source)

There are two real aspects to a pair bond. The first is the prosocial bit, the animal preferring to associate with one particular other animal. In voles, this requires the hormones oxytocin and vasopressin, and the neurotransmitter dopamine. But there’s another aspect to pair bonding: maintenance. And that requires more than fuzzy feelings, it also requires rejection of other potential mates, and guarding your mate against all comers. This aggressive behavior also involves dopamine, but in this case, a different population of receptors.

Dopamine is a neurotransmitter, which we often associate with the ‘rewarding’ properties of things. More properly, dopamine signaling in areas of the brain like the nucleus accumbens is associated with something that we scientists call “salience” or how much we need to be paying attention to something. Often this is associated with reward, you need to be paying attention if you want to win! But it’s also associated with other behaviors, like the formation and maintenance of pair bonds.

And dopamine is only as good as the receptors that are involved with it. In the case dopamine, the receptors are pretty simple, there are D1-like receptors and D2-like receptors (as opposed to serotonin, which has around 17 different types of receptor, all of which do different things). D1-like and D2-like receptors occur on different sets of neurons in the nucleus accumbens. This means that pair bond formation can rely mostly on D1-like receptor containing neurons, while the aggressive behaviors of pair bond maintenance can rely on the D2-like receptor containing neurons.

And the D2-like receptor containing neurons are themselves part of a network. In this case, they are part of a network which involves kappa opioid receptors. Opioid receptors are aptly named for their ability to bind things like the opiates (morphine, heroin, etc). But these receptors also bind ligands that are endogenous (they are made by the body and are normally present). And of course opioid receptors also come in different flavors, including mu (best known for pain killing abilities), and kappa.

The authors of this study wanted to look at the role of kappa opioid receptors on the aggressive behaviors that male prairie voles show during pair bond maintenance. To look at this, they gave doses of a kappa opioid receptor antagonist (nor-BNI), and then exposed pair bonded voles to an intruder in their cage.

The males are on the top and the females are on the bottom in the graphs above. You can see that the males will attach an intruder about half the time when they are pair bonded already. But when you give them a high dose of a kappa receptor antagonist, they decrease attacks. You’ll also note that this applies only to the males, the females have no effect. In contrast, doses of a mu receptor antagonist had no effect, showing that it’s not a general opiate receptor thing, it’s specific to the kappa receptors.

But where is this interaction taking place? The authors hypothesized that the kappa receptors that were important in aggressive behaviors would be those in the nucleus accumbens, the ones that would be able to influence the dopamine signaling that also plays a role in aggression. To look at this, they microinjected the kappa antagonist into several areas of the brain.

Here you can see the results of the microinjection on male and female aggressive behaviors in pair bonded voles. When they microinjected artificial cerebrospinal fluid (the control), there was no effect on aggression, the paired male voles attacked anyway. They also got no difference for the nucleus accumbens core or the ventral pallidum (the two sets of bars on the right). But when they microinjected the kappa antagonist into the nucleus accumbens shell region, the males and the females both ceased their attacks on intruders, suggesting that the kappa opioid receptors in the nucleus accumbens shell specifically (where they can have effects on dopamine receptor containing neurons) mediate the aggressive tendencies of the bonded voles. Kappa receptors are usually thought to mediate things like aversive states (like depressive like behaviors and anxiety), but it looks like, in this case, the kappa opioid receptors are partially responsible for inducing a suite of aggressive behaviors.

This is pretty interesting for a couple of reasons. First, it lets us know (as all people in long term relationships can attest) that there is more to a pair bond than just the formation, there is also maintenance, and that’s a separate set of behaviors than those first warm and fuzzy feelings. Secondly, this study gives us insight into the different mechanisms in the brain behind the maintenance of the pair bond. These may not be the same in humans (after all, we don’t start getting aggressive to every other person just because we have a partner), but it does show how different mechanisms can interact (kappa receptors and dopamine receptors), adding another step to the complexity of our seemingly simple behaviors.

Shanna L. Resendez, Morgan Kuhnmuench, Tarin Krzywosinski, and Brandon J. Aragona (2012). kappa-Opioid Receptors within the Nucleus Accumbens Shell Mediate Pair Bond Maintenance Journal of Neuroscience, 32 (20), 6771-6784 : 10.1523/JNEUROSCI.5779-11.2012

Scicurious About the Author: Scicurious is a PhD in Physiology, and is currently a postdoc in biomedical research. She loves the brain. And so should you. Follow on Twitter @Scicurious.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. aidel 11:17 am 08/27/2012

    This explains everything! I’ve got prairie vole hormones! (And I take opioids for chronic pain.)

    Link to this

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