Koob and others have used drugs to create the very same behavior in other lab animals. When the drugs are taken away from rats and mice, they display the same passive responses to elevated mazes. They withdraw socially. They mope. Human addicts do the same, Koob points out, mentioning characters in movies like Leaving Las Vegas and Trainspotting as examples.
To explain the physiology behind this passive depression state in the separated voles, Bosch checked their chemistry. The males separated from their mates had much higher levels of corticosterone, a stress chemical, in their blood than did any of the other groups, including voles separated from their brothers. Their HPA axis was working so hard, their adrenal glands weighed more. Bosch nailed CRF's role in driving both the HPA axis overdrive and the mopey behavior by blocking CRF receptors in the voles' brains. When he did, the divorced voles no longer hung limply from the sticks. They didn't float for as long in the water. They still remembered their mates, and were still bonded to them; they just didn't worry about it when they left them.
But here's the strange thing: both the voles who stayed with their female mates and the voles who were forced to split from the females had much more CRF in the BNST than did males who lived with, or were separated from, their brothers. In other words, loads of this stress-related hormone were being pumped in both the voles who got depressed after separation and voles who were still happily bonded and didn't show signs of passive-stress coping.
"Bonding itself produces high CRF," Bosch says. "But this does not mean the system is also firing." There is something fundamental about living with a mate that results in more CRF stress hormone in the brain, but that also prevents the engagement of the HPA stress axis as long as the mates stay together. Using an interesting metaphor for bonding, Bosch says "I compare it to a rifle. As soon as they form a pair-bond, the rifle is loaded with a bullet. But the trigger isn't pulled unless there is separation." He thinks that vasopressin serves as the chemical trigger to fire off the HPA axis during separation, though the exact roles of both oxytocin and vasopressin are still unclear.
Addicted drug users load the rifle, too. The gun won't fire unless they stop taking the drug. For the bonded voles, "it won't fire unless the partner leaves the nest," Bosch says.