Orbitofrontal cortex subregion inhibition during binge-like and aversion-resistant alcohol drinking

Area of Science:

• Neuroscience
• Behavioral Science
• Addiction Research

Background:

• Alcohol use disorder (AUD) and binge drinking are significant public health concerns.
• The orbitofrontal cortex (OFC) is crucial for decision-making and is affected by alcohol.
• Both medial (mOFC) and lateral (lOFC) OFC subregions are implicated in regulating alcohol-related behaviors.

Purpose of the Study:

• To investigate the distinct roles of the mOFC and lOFC in regulating binge-like and aversion-resistant ethanol drinking.
• To utilize chemogenetics to specifically inhibit neuronal activity in the mOFC and lOFC.

Main Methods:

• Employing a modified 'drinking in the dark' paradigm with C57BL/6J mice (male and female).
• Utilizing inhibitory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) hM4Di to suppress neuronal activity in mOFC or lOFC.
• Assessing the impact of chemogenetic inhibition on the consumption of ethanol, quinine-adulterated ethanol, water, and quinine-adulterated water.

Main Results:

• Inhibition of the mOFC did not affect ethanol consumption or aversion-resistant drinking.
• Chemogenetic inhibition of the lOFC led to increased ethanol consumption, but not preference.
• Neither mOFC nor lOFC inhibition altered the intake of water or quinine-adulterated water, confirming specificity to ethanol.

Conclusions:

• The lateral OFC plays a significant role in regulating alcohol consumption.
• The medial OFC does not appear to have a similar regulatory role in the tested ethanol consumption models.
• These findings contribute to understanding the neural circuitry underlying alcohol use and AUD.