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Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder

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Published on: June 23, 2023

Cellular prion protein (PrP(C)) modulates ethanol-induced behavioral adaptive changes in mice.

Daniel Rial¹, Pablo Pandolfo², Rafael M Bitencourt³

¹Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.

Behavioural Brain Research

|July 1, 2014

Summary

Cellular prion protein (PrP(C)) influences alcohol addiction by altering dopamine levels. Deleting PrP(C) impacts alcohol consumption and tolerance, suggesting PrP(C) is a target for addiction therapies.

Keywords:

Behavior Cellular prion protein (PrP(C))Consumption Dopamine Ethanol Rapid tolerance

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Area of Science:

Neuroscience
Addiction Research
Molecular Biology

Background:

Chronic drug use alters the brain's dopamine system, leading to addiction.
Cellular prion protein (PrP(C)) influences dopamine system homeostasis.
Understanding PrP(C)'s role in dopamine modulation may offer new addiction treatment targets.

Purpose of the Study:

To investigate the role of cellular prion protein (PrP(C)) in ethanol (EtOH) addiction.
To determine if genetic deletion of PrP(C) affects EtOH-induced behaviors and dopamine pathways.

Main Methods:

Utilized PrP(C) knockout mice to study EtOH consumption, drug seeking, and tolerance.
Measured dopamine levels and D1/D2 receptor density in specific brain regions.
Investigated the effect of dopamine D1 and D2 receptor blockade on EtOH consumption.

Main Results:

Genetic deletion of PrP(C) modulated EtOH-induced behaviors, including consumption and tolerance.
PrP(C) knockout mice showed reduced dopamine levels in the prefrontal cortex and fewer dopamine D1 receptors.
Pharmacological blockade of dopamine D1 receptors, not D2, reduced abnormal EtOH consumption in PrP(C) knockout mice.

Conclusions:

Cellular prion protein (PrP(C)) plays a significant role in the addictive properties of ethanol.
The PrP(C)/dopamine interaction is crucial for modulating ethanol addiction behaviors.
Targeting the PrP(C) pathway could offer novel therapeutic strategies for alcohol addiction.