Are you missing that special someone? To let him or her know you really care, nothing says 'I love you' like a lab report showing your corticotropin-releasing factor levels are elevated.

A paper published in Neuropsychopharmacology notes that evidence suggests social bonds have a positive impact on health and buffer against stressors. Absence or sudden disruption of those bonds can lead to anxiety-like and depressive-like disorders. "Thus," the authors say, "understanding the neurobiological consequences of partner loss, particularly with respect to increased susceptibility to depression, may be informative for developing strategies for coping with the loss of a loved one."

The hypothesis is that chronic CRF upregulation is important in the pathogenesis of these disorders. Reduced anxiety/depressive-like behaviors have been shown after blocking CRF receptors in rats as well as mice lacking CRF receptors.

Other studies have shown that social isolation itself affects passive stress-coping behavior, but what about the loss of a bonded partner? To examine the consequences of the disruption of a pair bond on the CRF system, Bosch et al. measured passive stress-coping as an indicator of anxiety/depressive-like behavior in male prairie voles (Microtus ochrogaster) following a three to five day separation from a female partner or a male sibling.

Is he a rat? That might be a good thing...

I had no idea what a prairie vole is, and why it was a suitable animal model for human relationship. The Smithsonian has a thorough section on the vole - apparently, voles are in the same family and order as rats, mice and lemmings. Hmm, using a male prairie vole, which is related to rats and lemmings, to predict male human behavior? Really, the jokes just tell themselves. (My personal favorite: the Beach vole, also known as Microtus breweri. Why can't I be named after a brewery? I suppose you could count the Breman, Germany-based Brauerei Beck&Co, maker of Beck's beer. Which I do.)

Anyway, the prairie vole is unique among mammals, and even among voles themselves - they appear to be monogamous, forming enduring and selective pair bonds. Ok, I'll buy that. Heck, humans have enough trouble doing that, so why not prairie voles? Even better, if you switch the v and l in vole, you get love. Aww.

Let's go for a swim

Male voles were paired with either unfamiliar females or male siblings. Apparently twenty-four hour co-habitation with a female, even without mating, is "sufficient for the induction of a partner preference, which is a laboratory proxy for pair-bond formation." After five days, half of the voles of each group were separated.

The authors conducted five experiments (see a nifty little summary graphic here). The first tested passive stress-coping behavior via the forced swim test. Passive stress-coping behavior is reflected as the amount of time the animal spends inactive - i.e. floating or immobile.

The time spent floating differed among groups (p=0.004). Males separated from a female partner displayed significantly more floating behavior than males remaining with their female partner, and males that either remained with or were isolated from their sibling partner. (See graphic here.)

In another experiment, the authors found that basal plasma corticosterone levels significantly differed among groups (p=0.04). Males separated from female partners had higher corticosterone levels than males that remained with the female partner (p<0.05), while in the sibling groups no differences were found. (More fun graphics here.)

Antidepressant drug manufacturers have new target audience: prairie voles

Ok, so male voles showed some stress-coping behavior and had higher CRF levels when separated from their female partners. What if you block the CRF system - will that alleviate symptoms?

The authors continuously infused a non-selective CRF-R antagonist, d-phe-CRF, beginning on the day of isolation. There were significant differences among groups in the forced swim test (p=0.004) and the tail suspension test (indicative of anxiety, p=0.0002). The antagonist-treated males separated from their partners showed reduced floating and immobility relative to vehicle controls, but there was no effect in antagonist-treated males who were not separated from their partners. (And yet another graphic here.)

Two caveats are important to consider when reading the article: "First, it is important to note that the present study does not differentiate the effects of pair bond disruption in general vs loss of a potential sexual partner. ... A second caveat is that the males in the paired group cohabitated with the females for several days longer than the males in the separated group."

All you need is vole, vole - vole is all you need

The results indicate, the authors say, that the CRF system may compliment reinforcing effects of other neuropeptide systems (e.g., oxytocin and vasopressin), which are thought to be critical to pair-bond formation. When CRF levels are elevated due to the loss of a mate, aversive emotional states - anxiety/depressive-like behaviors - are manifest. These behaviors can be blocked with CRF-R antagonists. (Interestingly, the authors note, there is growing evidence supporting use of CRF-R1 antagonists as antidepressants.) Ergo, the prairie vole model provides important insights into the psychopathological consequences of partner loss, with implications for bereavement in humans.

Next time I go on a business trip, I'll tell my significant other to avoid swimming or tail suspension.