Heightened histamine levels from inflammation inhibit the effects of the mood-regulating neurotransmitter serotonin in the brain. The corresponding research was published in the Journal of Neuroscience by researchers from Imperial College London and the University of South Carolina.
‘Inflammation’ is an umbrella term used to describe an immune response that triggers the release of histamine in the body. Once triggered, it increases blood flow to affected areas and delivers immune cells to help the body fight infections. The response, however, is not just triggered by infection. It can also be set off by stress, allergic reactions, and chronic conditions such as diabetes, obesity, and cancer, and has been linked to depression.
Serotonin is known as the ‘feel good’ neurotransmitter. It is the target of serotonin reuptake inhibitors (SSRIs). These drugs work by inhibiting its reabsorption into the brain. This then increases its availability in the brain and theoretically improves a person's mood. Not everyone, however, is responsive to these drugs, and there is strong evidence that patients with depression and severe inflammation are especially unlikely to respond to them.
This led researchers to investigate how serotonin, histamine, and SSRI’s interact. To do so, they created microelectrodes sensitive to serotonin and fitted them in the hippocampi of live mice. They then injected half of the mice with lipopolysaccharide (LPS) to induce inflammation. The other half were injected with a saline solution and kept as controls.
Via a technique known as fast-scan cyclic voltammetry (FSCV), the researchers measured serotonin levels in the brains of both groups of mice. Brain serotonin levels dropped within minutes of LPS injection, whereas there was no change among those injected with the saline solution. As LPS can not cross the blood-brain barrier by itself, the researchers say that their findings show how quickly inflammatory responses in the body can affect serotonin levels in the brain.
Upon further examination, the researchers found that the body's inflammatory response triggered the release of histamine in the brain, which then attached to inhibitory receptors on serotonin neurons and inhibited serotonin release.
In an attempt to counteract this process, the researchers gave the mice SSRI’s. In doing so, they found that serotonin levels in LPS-mice did not increase as much as in controls. They said this happened as the SSRIs increased levels of histamine in the brain, which canceled out any boost in serotonin. This was then confirmed upon administering histamine-reducing drugs to the LPS mice alongside SSRI’s as soon afterward, serotonin levels in LPS-mice rose back to control levels.
Further research is needed to see if these results translate over to humans. As humans have the same inhibitory receptors on serotonin neurons as mice, there is a reasonable chance that a similar pathway may exist in humans. If this is the case, the researchers say their findings could help diagnose depression by measuring histamine and serotonin levels in the brain. The findings could also help create novel treatments for depression that target histamine in the brain.