Drugs and the brain: A quick guide to brain chemistry
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
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
- 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
- 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
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,
Serotonin: Feeling groovy
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
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,
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
Picture: Addiction'. Published twice a year, 'Big Picture' is a
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Image: Dopamine crystals viewed with polarised light. Credit:
Spike Walker, Wellcome Images.