Case study: Showing how MAO A inhibitors reshape dopamine balance

Context, CNS and addiction biology
Service area, Synaptosome assays, transporter pharmacology, endogenous tissue

Curious how non nicotine tobacco constituents influence dopamine transporters and dopamine homeostasis via the dopamine transporter, DAT? In this study the authors wanted to see whether β carboline MAO A inhibitors that occur in tobacco could change DAT activity and, together with MAO inhibition, raise extracellular dopamine.

The challenge

Nicotine’s role in reward is well known, however the contribution of non nicotine smoke components is much less clear. The specific question here was, do β carboline MAO A inhibitors that are found in tobacco directly alter DAT function, dopamine uptake, and evoked dopamine release in brain tissue?

What we did

On behalf of the authors, the Gifford Bioscience team ran striatal synaptosome assays in physiologically relevant tissue to confirm the DAT effects that had been seen in their cell based DAT assays and in silico screening of tobacco compounds for MAO activity. In short, we:

• Measured [³H] dopamine uptake in endogenous tissue under controlled conditions.
• Measured evoked dopamine release to see the functional outcome.
• Aligned the tissue data with the authors’ cellular DAT assays and MAO profiling.

What stood out

1. Four MAO A inhibitors were clearly active, harman, norharman, harmaline and the newly highlighted 1 ethyl β carboline all emerged as potent modulators.
2. In cells, MAO A inhibitors reduced DAT activity in a dose dependent way, for example 1 ethyl β carboline showed an IC₅₀ of about 0.66 µM.
3. In synaptosomes, the same MAO A inhibitors decreased [³H] dopamine uptake and triggered marked dopamine release, confirming a dual effect, less enzymatic breakdown, and less reuptake, which together elevate extracellular dopamine.

Why it matters

For addiction biology, these findings help explain how non nicotine smoke components can reinforce dopaminergic signalling beyond nicotine itself. For drug discovery teams, it shows why it is useful to pair endogenous synaptosome workflows with targeted transporter assays so that the mechanism, the potency, and the real functional impact in tissue can all be seen, not just in overexpressing cell lines.

Read the publication paper here.

Working with Gifford Bioscience

Our customers work directly with our PI and PhD scientists, who design the study with you, run it in SOP driven conditions, and deliver data that is easy to take into internal review. Capabilities include radioligand binding, functional GPCR assays, transporter and synaptosome systems, and SPR screening, for CNS, oncology and metabolic programmes.

Talk to us

If you are exploring DAT, MAO, GPCRs, or transmitter systems in CNS, or if you want to move a similar project forward in oncology or metabolism, let us help you de risk the next step.