# The Effect of Serotonin 5‐HT2C Receptor Modulation on Binge Drinking and Alcohol‐Seeking in Female Mice

## TL;DR

This study shows that activating a specific brain receptor with lorcaserin can reduce binge drinking and alcohol-seeking in mice.

## Contribution

The study demonstrates that lorcaserin, a 5-HT2CR agonist, reduces alcohol consumption and seeking behaviors in mice.

## Key findings

- Lorcaserin significantly reduced alcohol consumption and seeking behaviors in mice.
- Positive allosteric modulators of 5-HT2CR did not significantly alter alcohol-related behaviors at tested doses.
- Targeting 5-HT2CR remains a valid approach for treating alcohol use disorder despite potential long-term concerns.

## Abstract

Alcohol misuse remains a leading cause of preventable death worldwide, prompting research into novel pharmacotherapies for alcohol use disorder (AUD). This study investigated the therapeutic potential of full agonism or positive allosteric modulation of the serotonin 2C receptor (5‐HT2CR) in addressing alcohol binge drinking and seeking behaviours in mice. Using a drinking‐in‐the‐dark paradigm and a context‐induced reinstatement model following punishment‐imposed abstinence, we assessed the acute effects of 5‐HT2CR ligands lorcaserin, CYD‐1‐79, VA012 and CTW0415 on alcohol intake and seeking behaviours in mice. Results showed that while lorcaserin effectively reduced both alcohol consumption and seeking behaviours, the 5‐HT2CR positive allosteric modulators (PAMs) did not significantly alter these behaviours over the range of doses examined. These findings suggest that 5‐HT2CR PAMs, at the tested doses, may lack intrinsic efficacy in modulating alcohol use. However, our lorcaserin data demonstrate that targeting 5‐HT2CR remains a valid approach to reduce behaviours associated with AUD.

Alcohol misuse remains a leading cause of preventable death worldwide, prompting research into novel pharmacotherapies for alcohol use disorder. Here we showed that lorcaserin, a potent serotonin 2C receptor (5‐HT2CR) agonist, effectively reduced alcohol consumption and seeking behaviours in mice. Despite concerns over potential off‐target effects with long‐term lorcaserin use, our data demonstrate that targeting 5‐HT2CR remains a valid approach to reduce behaviours associated with alcohol use disorder.