Published by Australian Academy of Science
Getting our heads around the brain Box 4 | Neurotransmitters and drugs

Imagine a drug that helps you study for a maths exam, or one that enhances memory in Alzheimer's sufferers. Australian scientists are in the race to develop such 'smart' drugs through research into neurotransmitters – the chemical messengers that convey impulses between neurons. They are also at the forefront of research on how imbalances in the cocktail of brain chemicals cause mental illnesses and even drug addiction.

What neurotransmitters do

Neurotransmitters are central to memory, learning, mood, behaviour, sleep, pain perception and sexual urge. They operate at the junctions between neurons, allowing communication between cells. When a nerve impulse arrives at the end of an axon, neurotransmitters are released, diffusing across a tiny gap to the next neuron. Here they bind to receptors – proteins on the surface of the cell – as a key fits into a lock. On delivery of their 'messages' these chemical couriers are destroyed or reabsorbed by the nerve endings in which they were produced.

Different neurotransmitters operate at different parts of the nervous system, and have different effects. Some promote the transmission of impulses while others inhibit it.

Involuntary nervous system neurotransmitters

Australian researchers played a major role in investigations into the neurotransmitters of the involuntary (or autonomic) nervous system which controls the gastrointestinal, cardiovascular, respiratory, excretory and endocrine system. The existing theory held that only two neurotransmitters, acetylcholine and nor-adrenalin, were involved in the control of internal organs. Max Bennett of Sydney University detected nerves that did not release either of these substances. Since there must be a chemical signal to relay the nerve impulse between adjacent neurons, this discovery started a race to identify the other transmitters involved.

More neurotransmitters are being found

Scientists have so far found hundreds of neurotransmitters, and the list is still growing. Neurotransmitters have an important role in the normal functioning of an individual. Research on neurotransmitters has brought greater understanding of some psychological diseases and this has led to more successful treatments. For example, we now know that manic depressive syndrome is a result of an imbalance in neurotransmitters, and we can correct the imbalance with drugs.

Specific neurotransmitters and their effects

The neurotransmitter serotonin plays a major role in emotions and judgement, and also sleep. Depression, suicidal behaviour, anxiety, impulsive behaviour and even eating disorders have been linked to serotonin imbalances. Recent research in Finland has suggested that murderers have very low levels of serotonin. Serotonin re-uptake inhibitors – a class of drugs including the well-known anti-depressant, Prozac – act by preventing the reabsorption of serotonin by the nerve endings. Illicit drugs including cannabis, Ecstasy and lysergic acid (LSD) also act on serotonin levels, producing feelings of euphoria.

The amino acids glutamate and GABA (gamma-aminobutyric acid) are the brain's most widespread neurotransmitters. They are involved in most facets of brain function, ranging from memory to sleep. They are also implicated in anxiety, and are the targets of drugs such as Valium and Mogadon.

David Curtis (John Curtin School of Medical Research) and his colleagues were the first to establish that these amino acids were neurotransmitters in the mammalian spinal cord and brain. They showed that GABA (and another amino acid, glycine) were the brain's major inhibitory transmitters whereas glutamate was the major excitatory transmitter. This work has had profound implications for the understanding and treatment of neurological disorders such as epilepsy and certain forms of spasticity.

Sydney University neuropharmacologist Graham Johnston has discovered a new class of GABA receptors involved in memory. He is designing a drug to stimulate the receptors, making them more responsive to GABA molecules. It is hoped that the drug will benefit Alzheimer's sufferers.

Meanwhile, Fred Mendelsohn, of the Howard Florey Institute of Medical Research in Melbourne, has discovered another brain chemical involved in memory. The chemical, a short chain of amino acids called a peptide, is either a neurotransmitter or a modulator, a substance that interacts with a neurotransmitter.

Imbalances in another neurotransmitter, dopamine, are implicated in Parkinson's disease. Dopamine's normal function is in regulating mood and movement. It is also involved in memory and schizophrenia.

Endorphins are neurotransmitters that relieve pain and induce euphoria. Athletes and gym junkies get a 'fix' of endorphins from excessive exercise. In the 1970s American scientists studying opium addiction discovered that morphine molecules lock into specific receptors in the brain. Endorphins, the brain's own morphine-like molecules, lock into these same sites.

Brain chemicals

One of the most recent finds is of a brain chemical aptly named anandamide after 'ananda', the Sanskrit word for bliss. Anandamide has a similar effect to tetrahydrocannabinol (THC), the active chemical in cannabis. THC locks into anandamide receptors in brain cells.

Scientists have recently discovered yet another natural brain chemical, nociceptin, which reduces anxiety. Mice injected with nociceptin become fearless, overcoming their terror of bright lights and open spaces.

Related sites

• Neurotransmitters and neuroactive peptides (Neuroscience for kids – University of Washington, USA)

• How do nerve cells communicate? (Society for Neuroscience, USA)

• Anandamide (Frostburg State University, Maryland, USA)

• Brain briefings: The opiate receptor (Society for Neuroscience, USA)

Other boxes

Box 1. The human nervous system

Box 2. Functions of the left and right sides of the brain

Box 3. Brain imaging