Get the low-down on some of the major chemicals that govern activity in our brains, how they work, and why certain drugs have the effects they do. By Barry Gibb.

Beneath every thought, dream or action lies a remarkable chemical dance. Molecules called neurotransmitters are in constant flux throughout the brain. Manufactured and released by the billions of neurons a human brain possesses, they bring order to human existence. But for the mind to work effectively, neurotransmitters need a port in which to dock - a receptor. Here, we'll take a look at some of the major neurotransmitters in the brain, their own special receptors and a few of the other chemicals, or drugs, that bind them.

Not sure what a word means? Check our glossary:

• Ion: An atom or molecule that has lost or gained electrons to become either negatively or positively charged.
• Ion channel: A protein or assembly of several proteins in a cell membrane that opens and closes to let ions move in and out of cells.
• Neuron: A nerve cell.
• Neurotransmitter: Chemicals made in the brain that pass signals between different nerve cells.
• Receptor: A protein or assembly of several proteins in a cell membrane that a molecule (such as a neurotransmitter, hormone or drug) can bind to.

 

Glutamate: What goes up...
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 (the same receptor ketamine blocks), kainate (a stimulant originally found in seaweed) and AMPA. Metabotropic glutamate receptors perform 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, MSG.

GABA: ...must come down
Not a reference to hardcore techno, GABA 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 (gamma-aminobutyric acid) receptors are split into two types. The 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 benzodiazapenes, are used in clinical contexts to help people get more sleep or lessen anxiety, for example.

Serotonin: Feeling groovy
Originally extracted from gut cells, serotonin has numerous roles throughout the body. Within the brain, however, it's become associated with 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 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 (also known as 5-HT or 5-hydroxytryptamine) receptors throughout the brain. Part of the reason behavioural complexity can arise from such apparent simplicity is due to the breadth of different serotonin receptor types and their downstream effects. 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 cause an increase in the overall levels of serotonin in the brain leading, in many cases, to diminished symptoms. Certain illegal drugs, such as MDMA ('ecstasy') and LSD ('acid') can also stimulate different serotonin receptors, leading to altered or extreme moods.

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 (and 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.

Dopamine: The pleasure principle
Without pleasure we would not be here. Eating, sex and happiness are all things that feel good - as a consequence, we seek them out. Of all the neurotransmitters in the brain, dopamine is the one most associated with pleasure. And with good reason - everything that makes you feel good is down to this key neurotransmitter and the effect it has on the brain. Moreover, every addictive substance known affects dopamine release in what's known as the brain's 'reward pathway', the equivalent of a neurological circuit connecting experience with feeling good.

Regulating dopamine's effects throughout the brain are its receptors, of which there are five known main variants: D1-D5. Alongside pleasure, these receptors ensure the involvement of dopamine in a range of activities, from movement to memory. Drugs, such as cocaine and amphetamines, lead to a sharp, temporary, rise in dopamine within the brain.

Cannabinoids: Natural highs?
It's no mystery that the brain responds to cannabis - the question is why would the brain evolve the ability to bind to this drug? Could it be the human body makes its own version of the plant-derived substance responsible for the effects of cannabis, tetrahydrocannabinol (THC)?

Endocannabinoids are the human version of what nature has created within certain plants. These fatty chemicals move freely between cells until they find their receptors. The two known ones are CB1 and CB2. Once activated, a number of pathways are activated, resulting in a diverse array of effects, from our experience of pain to movement of the digestive tract.

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 are taken to extremes by illegal drugs, such as heroin. The natural partners to the opioid receptors are the endorphins, released during certain activities, such as running (thought responsible for the 'runner's high'), pain and orgasm.

 

This article is part of the exclusive online content for 'Big Picture: Addiction'. Published twice a year, 'Big Picture' is a free post-16 resource for teachers that explores issues around biology and medicine. Find out more about the 'Big Picture' series.

 

Image: Dopamine crystals viewed with polarised light. Credit: Spike Walker, Wellcome Images.