Give a mouse a nasal spray of vasopressin and it chooses to drink less alcohol. Block any one of three receptors the hormone lands on, and the effect goes away.
That is the finding in a study published this month in Alcohol, Clinical and Experimental Research ↗. Vasopressin is best known as the body's water-retention hormone, the signal that tells the kidneys to hold on to fluid and nudges blood pressure up. The synthetic version is a hospital drug, sold as Vasostrict and Pitressin, used in shock and in diabetes insipidus for exactly that pressure effect. The point of putting it up the nose is to skip the blood vessels and reach the brain.
What they tested
The group worked with C57BL/6J mice in a two-bottle choice setup, the standard way to measure voluntary drinking: one bottle of water, one of ethanol, and a running tally of which the animal prefers. An earlier study from the same lab had shown intranasal vasopressin cut intake of sweetened ethanol. This one dropped the sweetener and asked whether the effect held for plain alcohol, and whether it survived when the mice were housed alone versus in groups.
It held. Intranasal vasopressin at 1.0 milligram per kilogram lowered ethanol intake in singly housed mice, and a higher 3.0 milligram dose did the same. In group-housed mice, the 3.0 dose also cut drinking. The route mattered as much as the molecule: the authors note that intranasal dosing did not move blood pressure or trigger the stress hormones that injected vasopressin sets off, which is the difference between a plausible drug and a dangerous one.
Three receptors, and which one carries it
Vasopressin does not act at a single address. It binds its own receptors, V1a and V1b, and also the oxytocin receptor, and the study used blocking drugs to work out which ones the alcohol effect runs through. In singly housed mice, pretreatment with a V1a, a V1b, or an oxytocin-receptor antagonist each weakened the drop in drinking, so all three were in play. At the higher dose the effect was pinned specifically to V1a: the V1a blocker SR-49059 erased it. In group-housed mice, blocking either V1a or V1b was enough to undo the effect, so social context appears to recruit the V1b receptor that solitary housing does not.
The higher dose also lit up the central nucleus of the amygdala, a region that sits at the intersection of stress and drinking, measured by c-Fos, a protein that flags recently active neurons. That is a correlation, not a wiring diagram, but it points at a circuit worth mapping.
Why a water hormone
Vasopressin and oxytocin are close chemical cousins, nine-amino-acid peptides that differ at two positions, and both have long been tied to social behavior and stress on top of their plumbing jobs. The vasopressin card ↗ on peptidemodel lists V1a ↗, V1b ↗ and the oxytocin receptor ↗ among its targets, which is exactly the set this study implicates. That breadth is the catch. A molecule that hits three receptors and helps run blood pressure, water balance, stress and bonding is not an obvious drug for problem drinking, and the intranasal trick is what makes it thinkable at all.
This is mouse work, and voluntary two-bottle drinking is a model of alcohol intake, not a model of alcohol use disorder in a person. But it lands a peptide-hormone approach next to the incretin drugs now being tested for the same problem, from a different receptor family and by a different route. The authors call it a potential target worth further investigation, which is the right size claim for what a nasal spray did to a mouse.