Neurotransmitters: eight chemical messengers

Glutamate: the accelerator

The brain's main excitatory ("go") signal: it pushes the next neuron toward firing, and it's involved in storing memories.

Involved in: Memory, learning. Effect on behaviour: Increased learning, enhanced memory.

• At NMDA receptors in the hippocampus, it's part of how new memories are stored.
• Too much is dangerous: it can excite cells to death, which is why it's cleared away so fast.

Drugs that act on it

• Ketamine (antagonist): Ketamine sits in the NMDA receptor and blocks it, the receptor the hippocampus needs to store new memories.
• Alcohol: Alcohol suppresses excitatory signalling like this, while it turns the brakes up.

Glutamate is go; GABA is stop.

GABA: the brake

The brain's main inhibitory ("stop") signal: it holds the next neuron back from firing.

Involved in: Brain function, sleep. Effect on behaviour: Decreased anxiety, decreased tension.

• It's found in high concentrations in the cortex and the limbic system, and it has a calming effect on the brain.
• Every neuron adds up its accelerator and brake inputs together, and that decides whether it fires.

Drugs that act on it

• Alcohol: Alcohol enhances inhibitory signalling. In the cerebellum it increases GABA release, which is part of why it makes you unsteady.
• Benzodiazepines: Benzodiazepines, such as diazepam and alprazolam, act on GABA's receptor and strengthen its effect. They're used for anxiety, sleep and seizures, but tolerance and dependence are real concerns.

GABA is stop; glutamate is go.

Dopamine: reward and movement

Learning, movement, reward and emotion; losing the neurons that make it is part of Parkinson's disease.

Involved in: Mood, sleep, learning. Effect on behaviour: Increased pleasure, suppressed appetite.

Where it comes from: Neurons in the midbrain: the substantia nigra, for movement, and the ventral tegmental area, for motivation.

• It drives wanting, the pull toward a reward, more than the pleasure itself.
• In rats, alcohol, nicotine, amphetamine and cocaine all raised dopamine in the nucleus accumbens.
• Parkinson's disease: the dopamine neurons of the substantia nigra are lost.
• Schizophrenia: certain symptoms are linked to overactive dopamine, and scans show the striatum making and releasing more of it.

Drugs that act on it

• Cocaine (reuptake inhibitor): Cocaine blocks the reuptake pumps for dopamine, norepinephrine and serotonin, so they stay in the gap.
• ADHD medication (reuptake inhibitor): Methylphenidate (Ritalin) blocks the dopamine transporter, so more dopamine stays in the gap.
• Antipsychotics (antagonist): Antipsychotics block dopamine's receptors without switching them on, all of them at the D2 receptor.
• Parkinson's medicine (agonist): Dopamine agonists stand in for dopamine at its receptors; levodopa is turned into dopamine by the brain.
• THC: Inhaled THC released dopamine in the striatum, something it shares with other addictive drugs.

Too little, in the substantia nigra: Parkinson's. Too much: linked to schizophrenia.

Serotonin: mood and sleep

Mood, sleep and memory; it's implicated in depression, and many psychiatric drugs act on it.

Involved in: Mood, sleep. Effect on behaviour: Modulated mood, suppressed appetite.

Where it comes from: Mainly the raphe nuclei, along the midline of the brainstem.

• Depression: the OpenStax textbook links it to low serotonin, and SSRIs are a common treatment, but a 2022 review of the main lines of research found no consistent evidence that low serotonin causes depression.

Drugs that act on it

• SSRIs (reuptake inhibitor): SSRIs, like Prozac, Paxil and Zoloft, stop serotonin being taken back up, giving it more time at its receptors.
• MDMA: MDMA makes the serotonin pump run backwards, so serotonin pours out of the neuron instead of being taken back in.
• Mushrooms (agonist): Psilocin, from mushrooms, switches on the 5-HT2A serotonin receptor itself; block that receptor and the trip doesn't happen.

Norepinephrine (noradrenaline): alert and ready

Alertness and arousal: the cells that supply it fire most when you're awake, and almost not at all in REM sleep (in rats).

Involved in: Heart, intestines, alertness. Effect on behaviour: Increased arousal, suppressed appetite.

Where it comes from: In the brain, the locus coeruleus above all; in the body, the sympathetic nerves.

• It's made by the sympathetic nerves, the system behind fight-or-flight: a faster heart, higher blood pressure, wider pupils, digestion put on hold.

Drugs that act on it

• Cocaine (reuptake inhibitor): Cocaine blocks the reuptake pumps for norepinephrine, dopamine and serotonin, so they stay in the gap.

Acetylcholine (ACh): muscles and memory

Carries the signal from nerve to muscle, and it's involved in memory.

Involved in: Muscle action, memory. Effect on behaviour: Increased arousal, enhanced cognition.

Where it comes from: Nerve endings where nerves meet muscles, the neuromuscular junction.

• At the neuromuscular junction, the nerve releases it and the muscle's receptors catch it: that's how a nerve tells a muscle to move.
• Myasthenia gravis: antibodies attack its receptors where nerves meet muscles, so the muscles weaken.
• Alzheimer's disease: medicines that raise acetylcholine levels can ease some symptoms for a while.

Drugs that act on it

• Nicotine (agonist): Nicotine switches on acetylcholine's nicotinic receptors itself; in the ventral tegmental area, that releases dopamine in the nucleus accumbens.
• Alzheimer's medicine: Donepezil, galantamine and rivastigmine raise acetylcholine levels, helping nerve cells communicate.

Endorphins: natural painkillers

The body's own opioids: they ease pain and help explain exercise euphoria.

Involved in: Pain, pleasure. Effect on behaviour: Decreased anxiety, decreased tension.

Where it comes from: Made mainly in the pituitary gland, and released in response to pain or stress.

• Sometimes they ease pain more than morphine does.
• They're behind the runner's high, and they're tied to the pleasure of laughter, love, sex and good food.

Drugs that act on it

• Opioids (agonist): Morphine, heroin and fentanyl bind the same receptors as endorphins, and switch them on.

Endorphins ease pain; substance P signals it.

Substance P: pain's messenger

Best known for its role in feeling pain.

Where it comes from: Pain nerves carry the signal from the skin to the spinal cord, where they release it.

• In the spinal cord, it's released together with glutamate, and it's thought to make the next neurons more sensitive to it, helping the pain signal on toward the brain.
• Drugs that block it are being studied for pain relief.

Substance P signals pain; endorphins ease it.