One way that brain cells communicate is through the passage of chemicals called neurotransmitters. Neurotransmitters carry messages across the space between brain cells known as the synapse. Their goal is to excite or inhibit neighboring cells by binding at their receptors (a process somewhat analogous to a lock and key). If the key fits, it activates the receptor, which impacts the electrical energy of that cell, thereby increasing or decreasing the chances of that cell releasing neurotransmitters of its own.


Excited cells are likely to continue the communication process by exciting other cells (the life of the party), while inhibited cells are likely to shut down (the wallflower). Whether a cell is excited or inhibited doesn’t necessarily translate into excited or inhibited behavior. Coffee, for example, provides a wakeful effect by inhibiting the actions of a chemical known as adenosine, which normally makes a person feel sleepy. By blocking adenosine, caffeine suppresses the message to feel sleepy, which leads to feeling alert and energized! In general, depressants (such as alcohol, Xanax, and anticonvulsants) have an inhibitory effect on brain cells, while stimulants (such as cocaine, Adderall, and ephedrine) are excitatory.


If a neurotransmitter doesn’t get a chance to bind, it can’t create any action. Therefore, medications and substances that allow neurotransmitters to hang out in the synapse longer essentially increase the chances that the neurotransmitters will successfully bind to receptors and enact change to neighboring cells (whether that is to excite them or inhibit them). At a basic level, antidepressants work by increasing the time neurotransmitters spend in the synapse – either through blocking their breakdown and/or their removal from the synapse.


Below are the 3 neurotransmitters most often impacted by antidepressant medications.
Serotonin plays a large role in many bodily functions, such as the sleep/wake cycle, sexuality, appetite, and mood. 95% of serotonin is actually located in the gut. That’s why antidepressant medications that increase the availability of serotonin often have significant gastrointestinal side effects!
Norepinephrine is a close cousin of epinephrine, otherwise known as adrenaline. As you might imagine from the name alone, norepinephrine helps regulate functions associated with the fight or flight response (“adrenaline rush”), including mental processes like attention and pain perception as well as bodily functions that help prepare the body to fight off an attacker or flee from it!
Dopamine is essential for control over our body movements as well as the sensations of pleasure and reward. Low levels or activity is associated with lack of motivation, fatigue, addictive behaviors, mood swings, memory loss, and difficulties with movement (e.g., Parkinson’s disease). On the other hand, too much activity is linked to symptoms of schizophrenia, such as hallucinations and delusions, so more is not always better!



Check in next week for How Antidepressants Work Part II: The Nitty Gritty where we’ll discuss the individual approaches various antidepressants use to address symptoms of depression. The following week in How Antidepressants Work Part III: Nonpharmacological Approaches we’ll explore other methods that have proven successful for the treatment of depression – with or without the use of antidepressant medications!