How to Make a Vole Fall in Love

It’s Valentine’s day (or at least, it was when I was writing this) and what Valentine’s day would be complete without articles of very dubious quality extolling the virtues of the neurohormone oxytocin (I can’t seem to avoid them anways)?  Oxytocin, for those who have been lucky enough to avoid these articles is a peptide (a small protein) and functions both as a neurotransmitter in the brain, and as a hormone circulating around the rest of the body.  Oxytocin actually does a lot of different things, but it is most famous for inducing social bonding, both romantic and otherwise.  No article about oxytocin is complete without a mention of the prairie vole, a rodent most widely known for forming a long term mated pairs which raise their litters of pups together, these pairs rarely divorce, and if the pairs are split up, voles don’t remarry.  Oxytocin is widely credited for making the prairie vole into a small fluffy paragon of romantic bliss.

Mated pairs of prairie voles, like this one, like to spend a lot of time in contact like this.

Except that vole love is rather more complicated than it seems and involves more than just oxytocin.  Aratonga et al¹, have found that if you really want to make a vole fall in love oxytocin shouldn’t be your target at all, what you want is a different neurotransmitter, called dopamine.

Actually convincing two voles to form a mated pair in the lab isn’t very difficult, just leave a male and a female vole in a cage together for twenty-four hours and they will mate and eventually form a pair bond.  The two are considered pair bonded when they both prefer their partner to other voles, and when treat all other voles aggressively.  If you don’t have twenty-four hours, you can speed up the process by activating the D2 dopamine receptors.

A quick aside about dopamine and its receptors.  Dopamine is a neurotransmitter and once released from a neuron, it can bind to several different kinds of receptors.  Which kind of receptor it binds to determines what dopamine makes the post-synaptic cell do, so dopamine binding to a D1 receptor can produce totally different response to dopamine binding to a D2 receptor, even though it’s all the same dopamine.

Male voles (this whole study focused on males) will very rapidly form a preference for a female if the D2 receptors in one part of its brain are activated, even if they haven’t mated yet.  For this to happen though the shell (the outer layer) of an area called the nucleus accumbens must be activated specifically.  A brain wide activation, or even one that occurs in the central core of the nucleus accumbens won’t work.  Activating the D1 receptors in the same area will actually block pair bonding.

Clusters of dots indicate the outer shell of the nucleus accumbens, This is where the dopamine receptor agonists and antagonists were injected during the experiment

This was determined using a set of drugs called D1 and D2 agonists and antagonists, which were injected into the shell of the nucleus accumbens.  Dopamine will bind to all the dopamine receptors in the area it is released, but these drugs will bind specifically to one receptor but not the other.  An agonist is a drug which turns a receptor on, while an antagonist turns it off, to recap:

D1 agonists activate D1 receptors

D1 antagonists deactivate D1 receptors

D2 agonists activate D2 receptors

D2 antagonists deactivate D2 receptors

D2 agonists can create a pair bond.  D1 agonists don’t create pair bonds, and when D1 and D2 agonists are injected together the D1 agonists will actually prevent the D2 agonist from creating a pair bond.  When a D2 agonist and D1 antagonist are injected together, however, pair bonding can occur.

So, the activity of different dopamine receptors in the shell of the nucleus accumbens can either promote or prevent pair bonding.  But when voles pair bond without the help of drugs they don’t have specific ways of activating just the D1 or just the D2 receptors, dopamine will act on them both.  We just saw that when these two are activated together pair bonding is blocked, so how do voles ever fall in love?

Well, the two receptor types aren’t actually activated together.  Which receptors a cell has isn’t static.  A neuron can alter which receptors are expressed on its surface, where they are expressed and how many of them there are, and this can drastically alter how that cell responds to a signal from one of its presynaptic neuron.  This is what happens to the male prairie voles.

Unpaired voles initially have lots of D2 receptors in their nucleus accumbens, and very few D1 receptors, so they initially form pair bonds with females when they are allowed to interact and mate for twenty-four hours.  Initially, even though these voles have a preference for their new mates, they aren’t fully pair bonded and will still approach other voles.  It takes about two weeks before they develop antagonism towards all other voles and are considered fully pair bonded.  Males which are fully pairbonded have about 60% more D1 receptors in their nucleus accumens than unpaired males, and blocking these receptors with D1 agonists blocks their aggression and weakens their bond with their mates.

So here is how voles fall in love.  When two unpaired voles meet they have lots of D2 dopamine receptors in the shell of the nucleus accumbens and activity of these receptors cause them to form a preference for their partner above all other voles.  As they continue to associate the numbers of D1 dopamine receptors increases.  The activity of D1 receptors blocks the activity of D2 receptors.  This means that in addition to preferring their mate, the voles also become aggressive towards other voles and this is permanent.  Once a vole has a mate, it almost never remarries for any reason because the D1 receptors are still there.  Essentially, its ability to form a new pair bond, or ‘fall in love’ has now been removed.  Voles have only one true love.

Is this how humans fall in love?  Probably not.  Despite the endearing resemblance to the first ten minutes of Up voles aren’t tiny fuzzy people and forming a monogamous pair bond is not in the strictest sense falling in love.  Also, although this will upset the makers of Valentine’s day cards and most romance novels humans aren’t actually monogamous.  If we were, serial dating, polyamory and the various forms of polygamy which have existed throughout human history would all be literally impossible.  So we probably don’t use this dopamine system for this purpose.

Animal studies are a wonderful, powerful, versatile research tool.  If they weren’t we’d have stopped doing them.  But figuring out to what extent the results of an animal study can be applied to people is hard and requires a lot of careful analysis.  We study vole pairbonding to learn about humans because there are a large number of behavioural analogues between human relationships and vole mated pairs and there are some shared neurological bases for those relationships, but we probably don’t cement long term relationships the same way voles do.  One of the reasons why the role of oxytocin in vole pairbonding gets more attention than the role of dopamine is that its much more directly relevant to people than the system studied in this article.

So remember, you are not a prairie vole, and unless you plan to fall in love with the first person you ever have sex with and spend the rest of your life attacking everyone you aren’t married to, don’t ask small monogamous rodents for relationship advice.  Some nice stories of human social bonding can be found here instead.  Its less rigorous, and its only behavioural, but since all behaviour is generated by neurotransmitter systems in our brains anyway, you might still pick up some good advice.

Happy Valentine’s Day.

References

1.        Aragona, B. J. et al. Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds. Nature neuroscience 9, 133–9 (2006).