SEROTONIN Now, onto the individual neurotransmitters. We’ll start with serotonin (also known as 5-hydroxytryptamine or 5-HT). Serotonin is a complex little guy because it has so many roles in your body. You probably are familiar with the idea that drugs that boost serotonin in the brain are used as antidepressants. However, serotonergic drugs have functions as diverse as treating migraine headaches (sumatriptan), suppressing appetite (fenfluramine), reducing nausea (ondansetron), and allowing you to go on trips with friends without ever leaving the room (lysergic acid diethylamide, or LSD). Serotonergic drugs also have wide-ranging adverse effects, including sexual dysfunction, diarrhea, and cardiac arrhythmias. How to make sense of it all? There are complex explanations for the various roles that serotonin plays in the body that reference each of the many 5-HT receptors (including 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7) found in different parts of the body. However, you are unlikely to be tested on the individual receptors, so for our purposes, you can simply remember that serotonin affects many DOMAINS within the body. Each of the major pharmacologic functions of serotonin have been packed into this word, as below: D is for Depression. Most (though not all) antidepressants involve serotonin in some way, leading to the conclusion that serotonin is likely involved in regulation of mood. O is for Obsession. There is strong evidence that serotonin plays a role in regulating obsessive thoughts and behavior. For example, if you were suddenly worried that you forgot to lock the door right before going to bed, you would go check the lock. When you see that it is in fact locked, your brain would use serotonin to help you feel “satisfied” that you were safe, and your sense of worry would go away. In people with obsessive-compulsive disorder (OCD), however, this “satisfaction” process has broken down, and they would return to continually check the lock many, many times. The role that serotonin plays in this process is perhaps even better understood than its role in mood, and the effect size of serotonergic medications in treating OCD is higher than it is for depression. M is for Migraines. While the exact mechanism remains incompletely understood, we know that medications which act on serotonin receptors in the brain can help to abort a migraine once it has started. A is for Anxiety. SSRIs and other medications that modulate serotonin, like buspirone (Buspar), are very helpful in the management of certain anxiety disorders like generalized anxiety disorder. I is for Intestines. The role of serotonin in the gut is often underestimated, even though 90% of all serotonin in your body is in the gastrointestinal tract. Serotonin drives gut motility, which is why many people on SSRIs experience diarrhea and general GI upset. N is for Nausea. Drugs like ondansetron (Zofran), which block serotonin, are effective at preventing nausea. S is for Sexual. Serotonin plays a large role in sexual functioning. Many people who take SSRIs report that their desire for sex, ability to maintain arousal, and capacity to reach orgasm are compromised. This side effect should not be ignored! Sexual side effects are the number one reason that someone stops taking an SSRI, so it’s an important thing to bring up before prescribing one. Serotonin’s pharmacologic functions cut across multiple DOMAINS: Depression Obsessions Migraines Anxiety Intestines Nausea Sexual As a brief aside, serotonin also affects platelet binding and adhesion, so there is a small risk of increased bleeding. However, several high quality studies have not shown any increase in clinically significant adverse outcomes in patients taking an SSRI, so there is no indication for actually changing your clinical practice based upon this minimal risk. (Ergo, it has been left out of the DOMAINS mnemonic.) NEUROANATOMY One bit of trivia that often gets tested is the fact that serotonin comes from the raphe nuclei in the brain. Why is this so important? No idea, but it does show up on tests, so here’s a handy mnemonic to help you memorize it. To connect the production of serotonin to the raphe nuclei, think of the Renaissance painter Raffaello Sanzio da Urbino, or Sir Raphael. Hello there. Serotonin is produced in the raphe nuclei. Think of Sir Raphael to link serotonin to the raphe nuclei. SEROTONIN SYNDROME Another way to remember the effects of serotonin is to look at what happens when your body has too much of it. There is a condition known as serotonin syndrome which can occur when two highly serotonergic drugs are taken at the same time. Patients with serotonin syndrome present with a characteristic constellation of symptoms which you can remember by the mnemonic Shits and SHIVERS: Shits is for Diarrhea. As would be expected given the role of serotonin in the gut, serotonin syndrome often causes severe diarrhea. S is for Shivering. This is fairly unique to serotonin syndrome and helps to distinguish it from other hyperthermic syndromes. H is for Hyperreflexia. Diffuse hyperreflexia and myoclonus are both frequently seen. I is for Increased temperature. Hyperthermia can be observed in severe cases. V is for Vital sign instability. Heart rate, respirations, and blood pressure are often abnormal and can fluctuate wildly. E is for Encephalopathy. Acute changes in someone’s mental status following a change in drug regimen can be a telltale sign of serotonin syndrome. R is for Restlessness. Increased motor activity, often uncoordinated, is often seen. S is for Sweating. Diaphoresis is an autonomic response to excessive serotonin. The severity of serotonin syndrome can vary. In lesser forms, it produces only mild discomfort. However, in its extreme forms, there is a significant mortality rate associated with this syndrome (between 2 and 12%), and many patients will require admission to the ICU. In fact, the 1984 death of 18 year-old college student Libby Zion from serotonin syndrome after she was prescribed two serotonergic drugs (phenelzine, a monoamine oxidase inhibitor, and meperidine, an opioid with significant serotonergic activity) by an overworked intern is what led directly to the federal regulations imposing work-hour restrictions during residency. Serotonin syndrome can be recognized by its Shits and SHIVERS: Shits (diarrhea) Shivering Hyperreflexia Increased temperature Vital sign instability Encephalopathy Restlessness Sweating DOPAMINE Like serotonin, dopamine has diverse functions throughout the body, including acting as a neurotransmitter in the central nervous system, inhibiting gastric motility, increasing urine output, and modulating blood vessel tone. These actions are mediated by various receptors, with D1, D2, D3, D4, and D5 receptor subtypes having been identified so far. For our purposes, we will primarily focus on dopamine’s effects in the central nervous system. Use the word DOPAMINE itself to remind you of this neurotransmitter’s many functions: D is for Drugs. Studies consistently show that the release of dopamine plays a strong role in how addictive a substance is. O is for psychOsis. Current evidence suggests that dysregulation of dopamine plays a key role in psychosis. In addition, medications that block dopamine seem to lessen some features of psychosis, such as delusions and thought disorganization. P is for Prolactin inhibition. Dopamine directly inhibits prolactin release. Therefore, when dopamine is blocked, a side effect can be hyperprolactinemia, causing breast development and milk release (even in males). A is for Attention. Drugs that boost dopamine, such as stimulants, can be used to improve attention and concentration. M is for Motivation. Dopamine governs motivation and reward. Anytime you think about doing an action to get some kind of a reward (whether that’s making food so you can eat it or studying for a test so that you can do well), dopamine is released. Interestingly, dopamine appears to influence only the “wanting” without affecting the “liking.” For example, a rat with a dysfunctional dopamine system will no longer seek out food, but if food is placed in front of it, the rat will still eat it and enjoy it. I is for Involuntary movements. Dopamine is involved in motor activity. It’s not as though dopamine directly causes muscle contraction (see: acetylcholine). Rather, dopamine makes movements more likely to happen. In this way, you can think of dopamine as being similar to grease: it doesn’t move the hinges, it just makes them easier to move. This explains why people under the influence of highly dopaminergic drugs like methamphetamine appear hyperactive with frequent purposeless movements. It also explains why patients with Parkinson’s disease (characterized by a loss of dopamine-releasing neurons) or who are taking dopamine-blocking drugs often have difficulty initiating movements (more to come on this in Chapter 4). N is for Nausea. For reasons that aren’t completely understood, drugs that block dopamine (such as prochlorperazine) are effective at reducing nausea. E is for Energy. Drugs that boost dopamine in the brain, like bupropion (Wellbutrin), are known to increase energy, which can be helpful in treating the neurovegetative symptoms of depression. The functions of DOPAMINE are: Drugs psychOsis Prolactin inhibition Attention Motivation Involuntary movements Nausea Energy Read this list a few times, then pack the information into that part of your brain labeled “Very Important.” Think about how well you want to do on the test or how much you want to impress others with your knowledge of psychopharmacology! By tying this information to future rewards, you are using dopamine to motivate you, and you will learn the information better. DOPAMINE RECEPTORS  Something that is occasionally tested is the fact that many antipsychotics work primarily on the D2 receptor subtype (abbreviated D2R). If you notice that D2R sounds a bit like detour, so you can think of a psychotic person taking a D2R from reality. Antipsychotics are thought to work by blocking the D2 receptor. Psychotic patients sometimes take a D2R from reality. NEUROANATOMY Dopamine’s various effects in the brain are a function of the multiple areas, or pathways, in which dopamine is active in the brain. While there are eight dopaminergic pathways, we will only review the highest-yield ones here.  First, the ability of antipsychotics to reduce positive symptoms in schizophrenia (such as hallucinations, delusions, and thought disorganization) appears to be related to its effects in the mesolimbic pathway. You can remember this association by thinking that you need limbs in order to do a “thumbs-up” sign (to indicate positivity). Blocking dopamine reduces positive symptoms via the mesolimbic pathway. You need limbs to show positivity with a thumbs-up! Second, the negative symptoms of schizophrenia (such as apathy, blunted affect, cognitive impairment, and poverty of thought) appear related to hypofunction of dopaminergic neurons in the mesocortical pathway. This association makes sense, as the higher thought processes that are impacted are localized in the cerebral cortex. Third, inhibition of prolactin is a function of dopamine’s effects in the tuberoinfundibular pathway, which you can remember as “this inhibits prolactin.” Dopamine inhibits prolactin via the tuberoinfundibular pathway. TuberoInfundibular Pathway = This Inhibits Prolactin Fourth, dopamine’s involvement in addiction and reinforcement stem from its presence in the reward pathway located in the ventral tegmental area. Drugs that act on this pathway (such as heroin and methamphetamines) are often highly addicting. The ventral tegmental area connects to the limbic system, which (as you will recall from neurology) contains many of the structures involved in emotion, learning, and memory. You can remember the association of the ventral tegmental area to drug addiction by thinking of the phrase “very tiring addiction.” Dopamine is involved in the reward pathway via the ventral tegmental area. Ventral Tegmental Area = Very Tiring Addiction Finally, dopamine’s effects on involuntary movements are due to alterations in the nigrostriatal pathway. These effects manifest themselves in three areas: extra-pyramidal side effects, stuttering, and Parkinson’s disease. Fortunately, these three functions can be packed away easily in the name of the pathway: the nigrostriatal pathway is involved in involuntary movements, stuttering, and parkinsonism. Dopamine’s effects on movement are linked to its role in the nigrostriatal pathway. NigroStriatal Pathway = iNvoluntary movements, Stuttering, and Parkinsonism NOREPINEPHRINE Norepinephrine, along with serotonin and dopamine, make up the group of neurotransmitters known as catecholamines. Catecholamines are key players in mediating the sympathetic nervous system and its associated “fight or flight” response. Of the three catecholamines, norepinephrine plays the largest role in mediating the physiologic signs and symptoms characteristic of sympathetic nervous system activation.  We can visualize the effects of sympathetic nervous system activation by imagining they we have just run into a large and threatening creature such as Cerberus (a three-headed demonic dog which guards the underworld in Greek mythology). In response to seeing Cerberus, your body will immediately go into sympathetic nervous system overdrive, releasing lots of norepinephrine into synapses (both centrally in the brain as well as peripherally) while injecting its counterpart epinephrine into the bloodstream to prepare your body for a “fight or flight” response. First, your brain would snap to the current moment, concentrating and focusing on what is at hand. You would get a burst of energy to enable you to fight (or flee, as the case may be). Peripherally, your body would prepare for battle by increasing your heart rate, raising your blood pressure to shunt blood to the most important parts of the body, mobilizing glucose, and putting less-essential services like eating, pooping, or peeing on hold. The sympathetic nervous system’s effects are largely mediated by norepinephrine. Remember fight or flight! NEUROANATOMY Let’s use our friend Cerberus to help us remember another fact about norepinephrine. Like serotonin and the raphe nucleus, the fact that norepinephrine is produced in the locus ceruleus is frequently tested. Norepinephrine is produced in the locus ceruleus. Seeing Cerberus would result in norepinephrine release from the locus ceruleus. ADRENERGIC RECEPTORS Norepinephrine mediates its effects via several receptors, including α-1, α-2, β-1, β-2, and β-3. Each of these adrenergic receptors plays a unique role, which comes into play when using the many drugs (both prescription and recreational) that involve norepinephrine. Pay close attention here, as differences in adrenergic receptor profiles mediate the differences in clinical effects between various drugs. α-1 adrenergic receptors are widely distributed throughout the body and mediate many of the effects of the sympathetic nervous system, including vasoconstriction, sweating, and mobilizing glucose into the blood stream. α-1 receptors are also responsible for the sympathetic nervous system’s effects in the brain. You can remember the widespread distribution of α-1 receptors by thinking that α-1 receptors are found α-11 over the place. α-1 adrenergic receptors mediate many of norepinephrine’s effects, both centrally and peripherally. α-1 receptors are found α-11 over the place. α-2 adrenergic receptors are unique in that they have a net effect of inactivating the sympathetic nervous system (rather than activating it as all the other adrenergic receptors do). This works physiologically as part of a negative feedback loop where release of norepinephrine not only signals the body to enter “fight or flight” mode but also prepares it for the inevitable cool down. You can remember this unique function of α-2 receptors by noting how α-2 looks like A–Z to remind you that they take the sympathetic nervous system from beginning to end (A to Z). α-2 receptors are unique in that they inhibit the sympathetic nervous system. α-2 takes the SNS from A–Z (it ends its effects).  Clinically, the primary effect that β-1 adrenergic receptors have is on the heart. Stimulation of β-1 receptors results in increased cardiac output by raising both heart rate and stroke volume. This is why β-blockers like carvedilol (Coreg) can be used for cardioprotection after a heart attack, as they decrease the workload on the heart. In contrast, the clinical effects of β-2 receptors are found primarily in the lungs where they work to relax the bronchioles, resulting in increased airflow. This is helpful physiologically, as both fighting and flying require oxygen. Clinically, β-2 agonists such as albuterol (Ventolin) work as treatments for asthma. Clinically, the effects of beta adrenergic receptors are localized primarily in the heart (β-1) and lungs (β-2). You beta have 1 heart and 2 lungs. The effects of β-2 receptors are unique in that they cause relaxation of smooth muscles in the bronchioles. In general, norepinephrine tends to cause constriction of smooth muscles (such as in blood vessels, the skin, and the gastrointestinal tract). You can remember this unique effect of β-2 receptors by thinking that “it’s β-2 relax.” β-2 receptors uniquely cause smooth muscle relaxation. It’s β-2 (better to) relax. ACETYLCHOLINE Like norepinephrine and its various receptors, the different effects of acetylcholine (often abbreviated ACh) are mediated by several types of receptors. For acetylcholine, the two classes of receptors are muscarinic and nicotinic receptors. Acetylcholine’s central role in the parasympathetic nervous system results from its interaction with muscarinic receptors, whereas nicotinic receptors are involved in mediating acetylcholine’s effects in the central nervous system and at the neuromuscular junction. You can remember the dual roles of acetylcholine by thinking of it as “I see two cholines.” Acetylcholine’s effects can be split on the basis of nicotinic versus muscarinic. Think of acetylcholine as I-see-two-cholines. MUSCARINIC RECEPTORS The parasympathetic nervous system and its associated “rest and digest” (or “feed and breed”) functions are directly mediated by the release of acetylcholine onto muscarinic receptors in peripheral organs. This makes acetylcholine a direct analog of norepinephrine in that the former carries out the will of the parasympathetic nervous system while the latter is governed by the sympathetic nervous system.  In this role, acetylcholine works to promote anabolic states by slowing the heart rate, focusing on digestion, allowing for elimination of waste (urine and feces), and increasing sexual arousal. Parasympathetic nervous system activation can be easily remembered in the classic mnemonic SLUDGEM, which stands for Salivation, Lacrimation, Urination, Diaphoresis, Gastrointestinal effects, Emesis, and Miosis. Use this mnemonic to recognize the signs of parasympathetic nervous system overactivation, which can occur in cases of drug overdose or exposure to certain pesticides or poisons. SLUDGEM syndrome should be treated promptly with an anticholinergic medication such as atropine (Atropen). The parasympathetic nervous system’s effects are largely mediated by acetylcholine. SLUDGEM: Salivation Lacrimation Urination Diaphoresis Gastrointestinal effects Emesis Miosis Just as the various adrenergic receptors each have their own functions, so too do the different muscarinic receptors (M1, M2, M3, M4, and M5) carry out different functions. However, for our purposes, they do not have to be memorized individually, as most psychoactive drugs target muscarinic receptors as a whole (as opposed to drugs that act on the sympathetic nervous system, which often target specific adrenergic receptors while sparing others.) As a take-away point, you can remember the association of muscarinic receptors by thinking of it as musky sludge. NICOTINIC RECEPTORS  When acting at nicotinic receptors, acetylcholine has two primary functions. First, acetylcholine acts as the neurotransmitter at the neuromuscular junction, diffusing across the synapse and causing contraction of skeletal muscles. This means that drugs which affect acetylcholine peripherally are used to treat neuromuscular diseases like myasthenia gravis. Second, acetylcholine’s effects in the central nervous system are mediated by nicotinic receptors. Acetylcholine is involved in multiple cognitive processes, including learning, memory, and attention. Clinically, this manifests itself in disorders such as Alzheimer’s disease, which is characterized by poor memory caused by damage to cholinergic neurons. You will also encounter nicotinic receptors in the context of smoking, as nicotine (naturally) exerts many of its effects via the nicotinic receptor (in addition to downstream effects on norepinephrine, dopamine, and opioid receptors). You can remember the primary functions of nicotinic receptors (acting at the neuromuscular junction and in the central nervous system) by visualizing a guy named Nic working out at the gym and using his muscle memory. Nicotinic receptors are responsible for acetylcholine’s role in muscle contraction and cognition. Visualize Nic using his muscle memory. NEUROANATOMY  The nucleus basalis of Meynert is a particularly acetylcholine-rich area of the brain, and damage to this region is seen in Alzheimer’s disease and other disorders characterized by memory dysfunction. To remember the association of memory and the nucleus basalis, picture a scene from a hypothetical action movie. The setting is the nuclear base of Meynert, where a stressed-out secret agent is sweating while trying to remember the codes to cancel a nuclear launch as a countdown timer ticks away behind him (less than 90 seconds left!). The nucleus basalis of Meynert is rich in acetylcholine and is involved in memory. Remember the nuclear launch codes on the nuclear base of Meynert. HISTAMINE When most people hear histamine, they think of allergies, not neurotransmitters. However, once you first see the effect of using diphenhydramine (Benadryl) to put a dog to sleep before a long car trip, you’ll never forget that histamine is also a neurotransmitter with significant effects on the brain and behavior. Drugs that antagonize histamine are also frequently used to decrease stomach production. You can remember the three clinically relevant functions of antihistamine by remembering that antiHIStAmines Help with Insomnia, Stomach acid, and Allergies. I is for Insomnia. Histamine’s mental effects primarily have to do with alertness and the sleep-wake cycle. The cerebral cortex depends upon a constant stream of histamine for activation, so once you cut off that supply (for example, by using an antihistamine), the cortex shuts down, and a subjective feeling of tiredness is produced. Many antihistamines such as doxylamine (Unisom) are available over-the-counter as sleep aids. St is for Stomach acid. H2 blockers such as cimetidine (Tagamet), ranitidine (Zantac), and famotidine (Pepcid) treat heartburn and gastroduodenal ulcers by suppressing stomach acid secretion by parietal cells in the stomach. A is for Allergies. Histamine is the central molecule involved in the inflammatory response to allergens. Blocking its release reduces the characteristic symptoms of allergies, including itching, skin rashes, and nasal congestion. Histamine antagonists are helpful for allergies, sleep, and acid reflux. AntiHIStAmines Help with Insomnia, Stomach acid, and Allergies.  Histamine’s role in allergies and stomach acid production occurs peripherally in the body, while its cognitive effects are located centrally in the brain. Because of this, different antihistamines can target different locations to have different effects. First generation antihistamines such as diphenhydramine work both peripherally and in the central nervous system, so they are used not only to combat allergies but also for their sedative effect. In contrast, newer antihistamines such as loratadine (Claritin) do not cross the blood-brain barrier and therefore only work peripherally, which is why they’re advertised as non-drowsy. OPIOIDS Opioids are a group of compounds that bind to the opioid receptors in the brain. There are many naturally occurring (or endogenous) opioids such as endorphins or enkephalins which help to regulate pain perception. A runner’s high is a well-known example of your body attempting to regulate pain perception in response to stress. However, there are many exogenous drugs which bind much more strongly to the opioid receptor, and these are used both clinically for pain control as well as recreationally for their narcotic effect. The human race enjoys opioids so much that entire wars have been waged over access to them. One example is the Opium Wars which took place in China in the 1800’ s. While opium wasn’t the only factor in the war, it can help us to remember the functions of opioids. Let’s focus on this one guy in the picture, an armed colonialist.   This ARMED Colonialist can help us remember the functions of opioids: A is for Analgesia. Analgesia, or pain relief, is a well-known function of opioids. R is for Respiratory depression. Opioids cause a slowing of the breathing rate, especially in higher concentrations. Mechanistically, opioids make the respiratory center in the brain stem insensitive to carbon dioxide, so death in opioid overdose is via Ondine’s curse, or simply forgetting to breathe. M is for Miosis. Miosis, or constriction of the pupils, is a classic sign of opioid intoxication. On boards and on wards, pinpoint pupils in an obtunded patient should have you considering opioid overdose as the cause. E is for Euphoria. Opioids cause a feeling of bliss and well-being, such as the runner’s high mentioned earlier. However, in some people, the desire for this feeling can become pathological and lead to states of addiction. D is for Drowsiness. Sedation and a significant slowing of mental functioning can occur with opioid use. C is for Constipation. Opioids cause constipation as a frequent side effect, so people taking opioids for chronic pain often need stool softeners to have a bowel movement. To remember the functions of opioids, think of an ARMED Colonialist: Analgesia Respiratory depression Miosis Euphoria Drowsiness Constipation OPIOID RECEPTORS Like most neurotransmitters, there are a variety of opioid receptors in the brain, including ☐, ☐, ☐, nociceptin, and ☐, each with their own functions. Morphine and most of the other opioids we will cover seem to exert their analgesic effect by binding to the mu (☐) receptor subtype. Try to remember mu for morphine. Many opioids exert their analgesic effect by binding to the mu opioid receptor. Mu for morphine! GABA The final two neurotransmitters we will go over are, in essence, the brain’s “on” and “off” switches. We’ll start with GABA, the “off” switch. When you hear GABA, think inhibitory. To embed this into your mind, picture the most boring lecturer you have ever had. Think about how they would just gab on and on. Next, picture yourself falling asleep while listening to this gabber. As you fall asleep, you relax both physically and mentally. You feel more at ease, and a feeling of calm overtakes you. Your muscles unclench, and your breathing slows. Any trace of anxiety is out of your mind, and you look like the exact opposite of someone having a seizure. If you can hold this image in your mind, you can remember the effects of GABA on the body.   By inducing calmness and relaxation, GABAergic medications such as barbiturates and benzodiazepines have proven useful for treating insomnia, anxiety, and agitation. Their inhibition of neuronal transmission has also made them helpful as anticonvulsants, both for management of an acute seizure (as with benzodiazepines) as well as prophylaxis (as with gabapentin or other anticonvulsants). GABA is the brain’s primary inhibitory neurotransmitter. GABA is like a gabber who just goes on and on and puts everyone to sleep. On a recreational basis, drugs that modulate GABA (like alcohol) are frequently used to reduce anxiety, as can be seen whenever someone pours themselves a drink to de-stress after a long day at work. Pharmacologically, GABA receptors are divided into two major subtypes (GABAA and GABAB receptors), each with their own functions. However, the precise distinction between these two subtypes is beyond the scope of this discussion. For our purposes, just know that activation of either subtype will generally result in the depressant effects mentioned above. GLUTAMATE In contrast to GABA, glutamate is excitatory. This means that glutamate binding to a post-synaptic neuron almost always leads to excitation of that cell. How this translates clinically is still unclear. It would be wrong to think that glutamate causes effects that are opposite to what is observed with GABA even though one is excitatory and the other is inhibitory. These terms refer specifically to the effect that these neurotransmitters have on the post-synaptic membrane, not to their more general cognitive and physiologic effects. For our purposes, just know that glutamate acts as an amplifier of neuronal signals and is involved in learning, memory, and processing thoughts and sensory inputs. Like many of the neurotransmitters we have discussed, glutamate binds to various receptors, each with their own functions. Specifically, glutamate can bind to NMDA receptors, AMPA receptors, kainite receptors, and metabotropic receptors. The exact effects of each of these receptors are still being elucidated (owing to the fact that glutamate’s role as a neurotransmitter came decades after the discovery of other neurotransmitters like serotonin, acetylcholine, and norepinephrine). The science on this neurotransmitter is young, so expect to hear more about it soon. Glutamate is excitatory and has effects on learning, memory, and thoughts. GlutaMATe is involved in Memory And Thought. CONCLUSION And that’s it for the neurotransmitters! There are many more neurotransmitters than this (in fact, it is currently estimated that there are between 80 and 200 different molecules used for signaling in the brain), but we’ll stick to the eight most clinically significant ones discussed here. Because they are so foundational to the study of psychopharmacology, take a moment to review each of the neurotransmitters we’ve discussed and try to embed them into your mind one more time.