Serotonin, a neurotransmitter, plays an important role in regulating mood and emotions. Low levels of serotonin in the brain stem have been linked to depression, anxiety, and other mood disorders. On the other hand, adequate levels of serotonin in the brain stem can contribute to feelings of happiness, satisfaction, and well-being. Serotonin is involved in regulating sleep, appetite, and other important functions, so it is important to maintain proper levels of this neurotransmitter to promote overall health and well-being.
New research into the opposing actions of serotonin-producing nerve fibers in mice could lead to the development of drugs to treat addiction and major depression. Scientists in Japan have discovered a nerve pathway in mice that is involved in the processing of rewarding and distressing stimuli and situations.
The new pathway, which originates in the median raphe nucleus, a bundle of nerve fibers in the brain stem, acts in opposition to a previously identified reward/aversion pathway that originates in the nearby dorsal raphe nucleus. The findings, published in the journal Nature Communications by scientists from Hokkaido University and Kyoto University with their colleagues, could have implications for developing drug treatments for a variety of mental disorders, including addiction and major depression.
These new findings could contribute to a better understanding of the biological basis of mental disorders characterized by abnormal processing of rewards and aversive information, such as drug addiction and major depressive disorder.
Yu Ohmura
Activating serotonin-producing nerve fibers from the dorsal raphe nucleus in the brain stem of mice results in the pleasurable feeling associated with reward, according to previous research. However, selective serotonin reuptake inhibitors (SSRIs), antidepressant drugs that increase serotonin levels in the brain, fail to produce clear feelings of reward and are ineffective in treating the loss of ability to feel pleasure associated with depression. This suggests that the brain contains additional serotonin-producing nerve pathways associated with feelings of reward and aversion.
To further study the reward and aversion nerve pathways of the brain, Hokkaido University neuropharmacologist Yu Ohmura and Kyoto University pharmacologist Kazuki Nagayasu, together with colleagues at several universities in Japan, focused their attention on the median raphe nucleus. This region has not received as much research attention as its brain stem neighbour, the dorsal raphe nucleus, even though it also is a source of serotonergic nerve fibres.
The researchers used fluorescent proteins to detect the entry of calcium ions, a proxy for neuronal activation in a cell-type specific manner, to measure the activity of serotonin neurons in mice in response to stimulating and inhibiting the median raphe.
Pinching a mouse’s tail, for example, increased calcium-dependent fluorescence in the serotonin neurons of the median raphe. Providing mice with a treat, such as sugar, reduced median raphe serotonin fluorescence. Furthermore, depending on the type of stimulus used, directly stimulating or inhibiting the median raphe nucleus using a genetic technique involving light resulted in aversive or reward-seeking behavior, such as avoiding or wanting to stay in a chamber.
The researchers also performed tests to determine where the switched-on serotonergic nerve fibres of the median raphe were sending signals, and they discovered an important connection with the brain stem’s interpenduncular nucleus. They also discovered serotonin receptors in this nucleus that were involved in the aversive properties of median raphe serotonergic activity.
More research is needed to fully understand this pathway, as well as others associated with rewarding and aversive feelings and behaviors. “These new findings could contribute to a better understanding of the biological basis of mental disorders characterized by abnormal processing of rewards and aversive information, such as drug addiction and major depressive disorder,” says Ohmura.
