Brain chemistry, drugs and diseaseEdexcel A-Level Biology A: Revision notes

Synapses use chemicals called neurotransmitters. Each brain pathway relies on a balance of these naturally occurring brain chemicals. If too little or too much is released, removed or detected, transmission is disrupted and disease can result.

Two examples:

• Dopamine: controls movement and reward. Too little contributes to Parkinson's disease.
• Serotonin: affects mood, sleep and appetite. Low levels in some synapses are linked with depression.

In Parkinson's disease, dopamine-releasing neurones in the substantia nigra (part of the basal ganglia) die. Less dopamine is released into synapses in the motor pathways, so the postsynaptic neurones are stimulated less.

Symptoms: tremor, rigidity and slow movement. The disease is progressive, as more neurones die over time.

Dopamine itself cannot be given because it cannot cross the blood-brain barrier. L-Dopa is a precursor of dopamine. It crosses the barrier and is converted into dopamine in the brain.

• Extra dopamine is released into the synapses, restoring stimulation of postsynaptic neurones.
• Symptoms improve, but L-Dopa treats the symptoms and does not stop the disease.
• As more neurones die, fewer remain to convert and release dopamine, so higher doses are needed over time.
• High doses cause side effects, e.g. involuntary movements and nausea.

Some people with depression have a lower concentration of serotonin in certain synapses. SSRIs (selective serotonin reuptake inhibitors), e.g. fluoxetine, bind to the reuptake transporter proteins in the presynaptic membrane. Serotonin is not taken back into the presynaptic neurone, so it stays in the cleft longer and stimulates the postsynaptic receptors more.

SSRIs help many but not all patients, and effects take weeks, so serotonin is likely to be one factor in depression and not the only cause. The link is a correlation.

MDMA has a similar shape to serotonin. It binds to the serotonin transporter proteins, blocks reuptake and causes extra serotonin to be released from presynaptic neurones. The concentration of serotonin in the cleft rises sharply, so postsynaptic neurones are overstimulated, causing euphoria and energy.

After the drug wears off, stores of serotonin are depleted, so less is released and the user may feel low in mood for days. MDMA also raises body temperature and can cause dehydration and, rarely, death.

Knowing how synapses work lets researchers design drugs that affect them, for example by blocking or mimicking a neurotransmitter, blocking its reuptake or breakdown, or supplying a precursor.

New drugs are tested in laboratory studies, then on animals, then in clinical trials on humans, often double-blind with a placebo, to check safety and effectiveness before being approved. Brain chemistry is complex, so drugs often have side effects.