Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain

Area of Science:

• Neuroscience
• Molecular Biology
• Addiction Research

Background:

• Early alcohol intoxication is a significant risk factor for developing addictive behaviors.
• Understanding the molecular mechanisms underlying acute ethanol intoxication is crucial for addressing addiction.

Purpose of the Study:

• To identify neuronal molecular correlates of acute ethanol intoxication.
• To investigate the role of mitochondrial trafficking in reward learning and addiction.

Main Methods:

• Quantitative mass spectrometry was used to screen over 2,000 hippocampal proteins in stable-isotope-labeled mice.
• Immunofluorescence analysis and two-photon in vivo imaging were employed to assess cellular and axonal changes.
• Genetic manipulation in *Drosophila* models was used to test the function of mitochondrial trafficking.

Main Results:

• Seventy-two synaptic proteins showed altered abundance after ethanol exposure, including mitochondrial and neuronal morphology proteins.
• A single ethanol intoxication induced lasting molecular, cellular, and behavioral changes in alcohol-naïve mice.
• Increased synaptic dynamics and mitochondrial trafficking in axons were observed, and its knockdown abolished conditioned alcohol preference in *Drosophila*.

Conclusions:

• Mitochondrial trafficking is implicated as a novel process in reward learning.
• High-resolution proteomics can effectively identify cellular mechanisms relevant to addictive behavior.
• Acute ethanol intoxication leads to significant and persistent changes in neuronal function and structure.