Which is the “molecule of happiness”?

Unfortunately, my period of depression is still on and despite few moments of calm and tranquility, as soon as something happens, I fall right back down into it and getting back to a positive view and to quiet seas were to swim happily before finally being able to touch dry land and get out of this horrible period seems very difficult in this moment.

I believe that, in this period of my life, thinking about the past is not helping me particularly, therefore I will leave aside for now the story of how I ended up doing a PhD in neuroscience in Germany and I will talk about the chemical messengers used by the brain to propagate signals in the brain (see this old post to understand how the signals in the brain are transmitted across neurons) and their modulators. And since I feel so down in this moment, I would like to explore the role of a neuromodulators that is commonly believed to be the contributor to feelings of well-being and happiness. So let´s talk about the serotonin.

Serotonin is a neuromodulator, that means it is a molecule able to modulate the transmission of information among neurons. By using the term modulating we imply that serotonin itself does not determine the presence of  synaptic activity,  but rather it makes this activity (when present) more or less strong. As I already very briefly wrote on my last post, the fast information transmission of the nerve impulse is determined by excitatory neurotransmitters, typically glutamate, and it is inhibited by inhibitory neurotransmitters, like GABA. Therefore, the neuromodulatory systems activate membrane proteins, called receptors, that act on the efficacy of the excitatory transmission, glutamaterigic or GABAergic, amplifying or decreasing it.

Serotonin is generally acting with an inhibitory action but, unfortunately, previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus and it has been implicated in practically every type of behaviour, such as appetitive, emotional, motor, cognitive and autonomic. Serotonin is synthesised from serotonergic neurons in the central nervous system (CNS) that are situated in one area of the brain and the neurons producing it send their projections in many different areas of the cerebral cortex (see picture below). However, serotonin is also synthesised from a particular type of cells in the gastrointestinal tract and in the respiratory system, where it acts by stimulating the smooth muscles and promoting peristalsis in the intestines (basically, promoting the movements our intestines use to digest food) and vasoconstriction in the blood vessels.

Schematic of serotonergic nuclei in the brain (highlighted in red) and their principal projections in the cerebral cortex and other brain areas.
Modified from “Serotonergic mechanisms in the migraine brain – a systematic review” by Deem et al., 2016. DOI: 10.1177/0333102416640501

In the CNS, from a physiological perspective, it is unclear whether serotonin affects behaviors specifically or more generally by coordinating the activity of the nervous system. However, it has been proven the role of serotonin in many psychiatric disorders, such as migraine, bipolar disorder, depression and anxiety, where drugs affecting serotonergic neurons and their receptors are used to treat such diseases. Indeed, researches show the important role of serotonin in this psychiatric disorder, since lesions of the serotonergic system produce aggressive and disinhibit behaviours, along with the analysis of the brains of suicidal individuals showing a lower number of serotonin receptors and decreased amount of serotonin.

Last but not least, some psychedelic drugs, such as LSD, psilocybin, mescaline and DMT, act on serotonin receptors: these serotonergic psychedelics have strong structural similarities to serotonin itself and, while their method of action is not fully understood yet, it is likely that they act by increasing excitation in the cortex, possibly by specifically facilitating input from the thalamus, the major relay for sensory information input to the cortex. On the other hand, amphetamines, and in particular MDMA, more commonly known as ecstasy, act by releasing serotonin from neurons, thus producing an accumulation of this neuromodulator in the brain, that will in turn make the person experience emotional communion, oneness, relatedness and emotional openness.

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