Welcome to the next episode of the WOrM Podcast 🪱

Today we’re looking at something surprisingly familiar in worm biology: alcohol.

But not just exposure — we’re talking about behaviour, tolerance, withdrawal, and how core neurotransmitter systems shape all of it.

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🧬 The central question

What actually happens when a worm is exposed to ethanol?

Not just in terms of movement — but across:

• behaviour

• lifespan

• neuronal signalling

• and gene expression

This study takes a multi-layered approach to understand how alcohol reshapes the worm.

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🔬 What they did

Worms were exposed to ethanol for 24 hours, followed by a withdrawal phase, and then tested in a behavioural assay — the classic diacetyl race.

This creates a simple but powerful 3-step model:

1. exposure

2. withdrawal

3. re-exposure

A framework that starts to look a lot like tolerance biology.

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🧠 What they found

The response to ethanol isn’t uniform — it depends on the nervous system.

• Wild-type worms show reduced lifespan at higher ethanol doses

• Dopamine (dop-3) and serotonin (tph-1) mutants respond differently

• Behaviour during chemotaxis is altered — not just slower, but less coordinated

• Re-exposure can rescue or worsen behaviour, depending on genotype

This is not just toxicity.

It’s state-dependent behaviour.

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⚡ Neurons are doing the work

At the cellular level, ethanol increases vesicle exocytosis in both dopaminergic and serotonergic neurons.

So the system is not shutting down — it’s being actively rewired.

And importantly, intact dopamine and serotonin signalling are required for normal responses to ethanol.

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🧪 The molecular layer

Ethanol exposure also shifts gene expression:

• Stress response genes like gst-4 and sod-3 are altered

• Metabolic genes like adh-1 are downregulated

• The response differs depending on dopamine and serotonin function

So behaviour, neurons, and metabolism are all coupled.

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🧠 The take-home message

Ethanol in C. elegans is not just a stressor.

It’s a probe.

A way to reveal how:

• neurotransmitters

• behaviour

• and metabolism

interact at the whole-organism level.

And the key point?

You don’t get the phenotype without the network.

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📄 Paper discussed

Rubio-Tomás, T.; Hunn, C. A.; Hajdú, G.; Sőti, C.; Tavernarakis, N.; Barta, C. (2026)

Specific genes of the dopaminergic (dop-3) and serotonergic (tph-1) pathways contribute to the effects of ethanol consumption in Caenorhabditis elegans

PLOS One, 21(3): e0344966

DOI: 10.1371/journal.pone.0344966

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📩 More info:

🔗 www.veerenchauhan.com

📧 veeren.chauhan@nottingham.ac.uk