Key Neurotransmitters

Why This Matters

Neurotransmitters are the chemical language your brain uses to communicate—and they're the primary target of nearly every psychoactive drug you'll study in this course. When you understand how these molecules work, you'll understand why cocaine feels different from alcohol, why SSRIs take weeks to work, and why withdrawal can be so brutal. You're being tested on the mechanisms behind drug action, addiction, and mental illness, and neurotransmitters are ground zero for all of it.

Don't just memorize which neurotransmitter does what. Know the balance between excitation and inhibition, understand how the reward pathway drives addiction, and recognize how monoamines became the foundation for psychiatric medication. Every drug you study will either mimic, block, or alter the release and reuptake of these chemicals—so master them now, and the rest of the course clicks into place.

---

Excitatory vs. Inhibitory: The Brain's Gas and Brake

Your brain maintains a delicate balance between neurons that fire and neurons that stay quiet. Too much excitation causes seizures and cell death; too much inhibition causes sedation and coma. This balance is the foundation for understanding depressants, stimulants, and why mixing them is dangerous.

Glutamate

• Primary excitatory neurotransmitter—responsible for the majority of fast synaptic transmission in the brain
• Essential for learning and memory through a process called long-term potentiation (LTP), which strengthens synaptic connections
• Excess glutamate causes excitotoxicity—neuronal death linked to Alzheimer's disease, stroke damage, and the neurotoxic effects of certain drugs

GABA (Gamma-Aminobutyric Acid)

• Primary inhibitory neurotransmitter—reduces neuronal firing and counterbalances glutamate's excitatory effects
• Target of depressant drugs including alcohol, benzodiazepines, and barbiturates, which enhance GABA activity to produce sedation
• Dysregulation linked to anxiety and seizures—too little GABA activity underlies panic disorders and epilepsy

Glycine

• Inhibitory neurotransmitter in the spinal cord and brainstem—critical for motor control and reflex modulation
• Co-agonist at NMDA receptors—works alongside glutamate to regulate excitatory transmission in higher brain regions
• Involved in pain processing—glycine receptor dysfunction affects chronic pain conditions and is a target for some anesthetics

---

The Monoamines: Mood, Motivation, and Medication

Monoamine neurotransmitters share a similar chemical structure and are the primary targets of antidepressants, antipsychotics, and stimulants. Dysfunction in monoamine systems underlies most major psychiatric disorders, making this category essential for understanding psychopharmacology.

Dopamine

• Central to reward and motivation—released during pleasurable activities and reinforces behaviors that lead to survival
• Primary target in addiction—drugs of abuse hijack the dopamine reward pathway, particularly in the nucleus accumbens
• Imbalances cause movement and thought disorders—too little dopamine in motor areas causes Parkinson's; excess activity in limbic areas is linked to schizophrenia

Serotonin

• Regulates mood, emotion, and impulse control—often called the "mood stabilizer" neurotransmitter
• Target of most antidepressants—SSRIs work by blocking serotonin reuptake, increasing its availability in the synapse
• Influences sleep, appetite, and aggression—low serotonin is associated with depression, anxiety, and impulsive behavior

Norepinephrine

• Drives arousal and the stress response—functions as both neurotransmitter and hormone in the fight-or-flight system
• Enhances attention and vigilance—targeted by ADHD medications and some antidepressants (SNRIs)
• Dysregulation contributes to mood disorders—both depression and anxiety involve norepinephrine system dysfunction

---

Acetylcholine: The Learning and Movement Molecule

Acetylcholine was the first neurotransmitter discovered and operates in both the central and peripheral nervous systems. It's essential for memory formation and voluntary muscle control, making it relevant to both cognitive disorders and drug effects on the body.

Acetylcholine

• Critical for memory and attention—the cholinergic system in the hippocampus and cortex supports learning and cognitive function
• Controls voluntary muscle movement—acetylcholine released at neuromuscular junctions triggers muscle contraction
• Depletion linked to Alzheimer's disease—cholinergic neurons die early in the disease; acetylcholinesterase inhibitors are a primary treatment

---

Neuromodulators: Fine-Tuning the System

Some chemical messengers don't simply excite or inhibit—they modulate how neurons respond to other signals. These neuromodulators often act more slowly and diffusely, influencing mood, pain perception, and arousal states.

Endorphins

• The body's natural opioids—bind to the same receptors as morphine and heroin to reduce pain perception
• Released during stress, exercise, and pain—responsible for "runner's high" and the body's built-in pain management system
• Opioid drugs mimic endorphin effects—understanding endorphins explains both opioid euphoria and the severity of withdrawal

Histamine

• Regulates wakefulness and arousal—histamine neurons in the hypothalamus promote alertness and attention
• Antihistamines cause drowsiness—blocking histamine receptors in the brain explains why allergy medications make you sleepy
• Influences appetite and immune function—plays roles in both central nervous system activity and peripheral inflammatory responses

Substance P

• Primary pain signal transmitter—carries pain information from peripheral nerves to the spinal cord and brain
• Links physical and emotional pain—elevated in both chronic pain conditions and depression, explaining their frequent co-occurrence
• Target for pain management research—Substance P antagonists are being developed as novel treatments for pain and mood disorders

---

Quick Reference Table

---

Self-Check Questions

1. Which two neurotransmitters represent the brain's primary excitatory and inhibitory balance, and why is this balance critical for understanding how depressants work?

2. Compare dopamine and serotonin: How do their roles in mood regulation differ, and which class of drugs primarily targets each?

3. If a patient has Alzheimer's disease, which neurotransmitter system is most affected, and what type of drug might be prescribed to address this deficit?

4. Explain why opioid drugs produce both pain relief and euphoria by referencing the neurotransmitter they mimic.

5. An FRQ asks you to explain why benzodiazepines reduce anxiety while cocaine increases alertness. Which neurotransmitter systems would you discuss for each drug, and what is the mechanism of action?