Dopamine Of all the neurotransmitters in the brain, dopamine is the one most associated with pleasure (though endorphins also play a large part). Everything that makes you feel good is down to dopamine and the effect it has on the brain. Moreover, every known addictive substance affects dopamine release in what’s known as the brain’s ‘reward pathway’, the equivalent of a neurological circuit connecting experience with feeling good.
Some research suggests that we shouldn’t think about dopamine as a ‘pleasure’ stimulator, but rather as a ‘motivation’
Drugs, such as cocaine and amphetamines, lead to a sharp, temporary rise in dopamine within the brain.
Depression and schizophrenia are two of the many mental illnesses that a physician can treat with effective medications. Knowing how medications work can increase your understanding of mental illness and encourage compliance—that is, consistently sticking to your medication treatment plan so that the medications are given a chance to be effective. This article will explain how antidepressant and antipsychotic medications work in the brain to treat these disorders.
How our brains work
The central nervous system (CNS), made up of the brain and spinal cord, controls our actions, thoughts and emotions. These functions are controlled by chemicals called neurotransmitters.† Neurotransmitters travel between different regions of the brain via nerve cells called neurons.
There are several different neurotransmitters that act on parts of these nerve cells called receptors. This produces effects that can influence memory, emotion, voluntary movement of muscles, appetite, temperature regulation and more.
problem substance use (i.e., alcohol and other drugs). Depression also often co-occurs with other mental illnesses, including bipolar disorder, schizophrenia and anxiety disorders.
Whatever the trigger, it is believed that the underlying biological basis of depression is a depletion in the levels of neurotransmitters such as serotonin, norepinephrine, and/or dopamine in the central nervous system.
All antidepressants† work in a similar way, though there are various types of antidepressants—often called “families”—that each work a bit differently. They all, however, increase the brain’s concentration of various neurotransmitters.
Schizophrenia is associated with an increase in dopamine activity in an area of the central nervous system called the mesolimbic pathway. The mesolimbic pathway is one of four major dopamine-related pathways in the brain that is associated with pleasurable feelings, with addiction—and with psychosis.
Generally speaking, antipsychotic medications work by blocking a specific subtype of the dopamine receptor, referred to as the D2 receptor.
Note that antipsychotic agents are also prescribed to treat other conditions apart from schizophrenia. This is referred to as “off-label”† prescribing and includes conditions such as Tourette’s syndrome, substance abuse (e.g., cocaine and methamphetamine), stuttering, obsessive-compulsive disorder, post-traumatic stress disorder, depression, bipolar disorder and personality disorders.
Clearly, depression and schizophrenia are very complex and debilitating disorders. Fortunately, medications like antidepressants and antipsychotics can help treat the core symptoms.
Glutamate is the brain’s ‘on switch’. Known as an ‘excitatory neurotransmitter’, this tiny molecule does pretty much what it says on the tin – wherever it finds a receptor to dock with, it causes the hosting neuron to become excited. An excited nerve is one that’s more likely to ‘fire’, resulting in the release of its own unique mix of neurotransmitters.
Glutamate receptors are a varied bunch, and can be split into two main families. Ionotropic receptors are so-called because they form channels for ions to move through when glutamate binds to them. Ionotropic glutamate receptors are: NMDA (which ketamine binds to and blocks its activity), kainate and AMPA.
Metabotropic glutamate receptors act a little more indirectly. Chances are, you’re already an expert on glutamate as it crops up in foods either alone (it tastes savoury), or in its flavour-enhancing form – monosodium glutamate, or MSG.
GABA (gamma-aminobutyric acid) is the neurotransmitter acting as glutamate’s lazy twin, its sole purpose being to slow things down, dampen and inhibit nervous activity. Like glutamate, the GABA receptors are split into two types. GABA A receptors respond to GABA binding by allowing the flow of ions across nerve membranes. The GABA B receptors involve intermediaries in the process.
Drugs that stimulate these receptors tend to slow the brain down, so it’s no surprise to discover alcohol affects these receptors. Drugs activating GABA receptors are found everywhere – liquid ecstasy, or GHB, has become well known as a ‘date rape drug’ while other activators, such as the benzodiazepines, are used in clinical contexts to help people get more sleep or lessen anxiety. These drugs are easy to overdose on, and produce tolerance (ie you need to take more and more to achieve the same effect). This means they aren’t used as much as they could be clinically, because they’re quite dangerous.
Serotonin: Feeling groovy
Ninety-five per cent of the body’s serotonin is actually in the gut, but the 5 per cent in the brain has a big effect on mood – a person’s overall state of mind, how they feel about themselves and the external world at a point in time. As you might expect, laying the burden of something as complex as mood on a single molecule could be oversimplifying things a little, but remarkably, this simple molecule does have a big impact on your mind.
The link between serotonin and how you feel is down to the large variety of serotonin receptors throughout the brain. Part of the reason the behavioural effects of this single neurotransmitter can be so complex is due to the number of different serotonin receptor types and the range of effects they can have.
These effects include causing the levels of numerous other neurotransmitters to be increased or decreased throughout different brain regions. Like a throwing a pebble into a lake, serotonin causes ripples of effect.
A lack of serotonin in the brain is associated with depression, which is why drugs called SSRIs (selective serotonin reuptake inhibitors), such as fluoxetine (Prozac), are commonly prescribed to help treat depression. Such drugs can cause an increase in the overall levels of serotonin in the brain leading, in many cases, to diminished symptoms.
Certain recreational drugs, such as MDMA (ecstasy) and LSD (acid), can also stimulate serotonin receptors, leading to altered or extreme moods. MDMA has two major effects on serotonin: causing it to be released as well as blocking the receptors involved in its reabsorption, meaning higher levels of serotonin remain in the synaptic cleft. This means that other receptors for serotonin continue to be active, creating the feeling of extreme happiness that MDMA is known for. However MDMA also depletes the levels of serotonin in the brain, at least in the short term. This is likely responsible for the ‘comedown’ phenomenon; after the positive effects of the drug wear off, many users are left feeling down.
LSD has a very similar structure to serotonin, meaning that it fits into and activates certain serotonin receptors. This means that brain processes related to serotonin release are constantly activated, producing feelings of happiness. LSD also affects many other areas of the brain to produce its other, psychedelic effects.
Acetylcholine: Remember me?
Among other things, acetylcholine appears to play an important role in learning and memory. The neurons that produce this neurotransmitter – cholinergic neurons – are found in several regions of the brain, where, when stimulated, they release their stores of neurotransmitter onto waiting neurons. But to have any effect, those neurons need to have the right receptors: in this instance, the nicotinic and muscarinic receptors.
Nicotinic receptors, named after one of their most potent activators, nicotine (the reason cigarettes are so addictive), allow ions to quickly pass through them when either acetycholine or nicotine binds to them. Muscarinic receptors (from muscarine, a receptor stimulant and poison extracted from certain mushrooms) act on a slower time frame than the nicotinic receptors. One of the most common blockers of the muscarinic receptors is atropine, a natural compound found in certain plants, such as deadly nightshade or mandrake.
Cannabinoids: Natural highs?
There’s no doubt that the brain responds to cannabis – the question is why would the brain evolve the ability to bind to this drug? In fact, the active component of the cannabis plant (tetrahydrocannabinol – THC) is a natural mimic of compounds that the human body actually makes on its own.
This group of THC-like chemicals made within the body are endocannabinoids. These are fatty chemicals able to move freely between cells until they find their receptors – CB1 and CB2. Once these are activated, a number of pathways are activated, resulting in a diverse array of effects, from reduced experience of pain to movement of the digestive tract, as well as having an effect on mood.
Opioids: Poppy-derived painkilling
The colourful poppy is the source of the alkaloid drug, opium (an opiate – literally meaning ‘poppy tears’), a property that led to the eventual discovery of the numerous opioid receptors that bind such compounds within the nervous system. One well-known opiate commonly used today for the treatment of severe pain is morphine (after Morpheus, the Greek god of dreams).
Distributed throughout the nervous system, the opioid receptors, OP1–OP4, are involved in all of the calming effects we might expect, such as pain relief and reduction in anxiety – but these are taken to extremes by recreational drugs such as heroin. The natural partners to the opioid receptors are the endorphins, released during certain activities, such as running (they’re thought to be responsible for the ‘runner’s high’), pain and orgasm.
DMT – Researchers speculate the illegal hallucinogen is released in our brains through the pineal gland during birth, death, and dreams.