The role of serotonin in the orbitofrontal cortex in alcohol consumption

Binge alcohol consumption poses a significant public health threat that greatly raises the risk of developing alcohol use disorder (AUD). Researchers aim to understand the neural circuitry involved in behaviors like continued drinking despite negative consequences in order to explore potential novel treatments for AUD. Serotonin, a neurotransmitter, has shown promise in both human studies and animal models in relation to alcohol consumption.

The orbitofrontal cortex (OFC), a brain region that both receives serotonergic input and is implicated in AUD, is of particular interest in this research. However, the impact of volitional alcohol consumption on serotonin signaling within the OFC and how this contributes to alcohol-related behaviors remains unclear. This study sought to investigate how a history of alcohol consumption affects the ability of serotonin (5-HT) to hyperpolarize OFC pyramidal neurons in mice and monkeys.

The results showed that a history of binge alcohol consumption decreases the expression of the 5-HT1A receptor, but not the 5-HT2A receptor, in the OFC of mice. Deletion of the 5-HT1A receptor from the OFC in mice led to increased alcohol intake and preference, particularly in males, but not females. Moreover, mice with the 5-HT1A receptor deleted exhibited increased quinine-adulterated alcohol intake, a measure of aversion-resistant drinking, in both males and females.

The study concludes that serotonin signaling in the OFC is a crucial target for modulating binge and compulsive alcohol consumption.