Serotonin (5HT) plays a key role in regulating brain function and behaviour, and disruptions to this system are associated with alcohol use disorders (AUD). The anterior cingulate cortex (ACC) and the central nucleus of the amygdala (CeA) are involved in the mechanisms underlying AUD and undergo functional changes in serotonin signalling following episodes of excessive alcohol consumption. However, understanding of real-time 5HT dynamics in these structures remained limited. The researchers hypothesised that binge drinking causes region-specific disruptions in 5HT dynamics during the processing of both positive and negative stimuli.
Methods and main findings
Using fibre photometry with the GRAB5HT sensor, the scientists identified distinct patterns of serotonin signalling associated with reward and avoidance in the ACC and CeA. Consumption of alcohol and other tastants suppressed the GRAB5HT signal in the ACC and increased the 5HT signal in the CeA. By contrast, aversive stimuli elicited similar increases in 5HT in both structures.
The effects of binge drinking on 5HT function proved unexpectedly varied. Disruptions in serotonin signalling specific to brain region, sex and stimulus type were identified and varied considerably over the weeks following the onset of alcohol consumption. This indicates that adaptations in serotonin signalling are specific to the neural circuits underlying different functions.
Optogenetic stimulation of 5HT terminals in the ACC and CeA increased avoidance behaviour without producing overt reward or aversion. Stimulating 5HT release in the ACC reduced alcohol consumption. Together, these findings identify distinct patterns of serotonin signalling associated with reward and avoidance in the ACC and CeA, which exhibit time-dependent shifts in their dynamics following binge drinking.
Significance of the study
The findings highlight the complexity of alcohol’s effects on the brain’s serotonin system. The differences identified in how the ACC and CeA respond to various stimuli, together with the influence of sex, indicate the need for a more nuanced approach to understanding and treating alcohol use disorders. The ability to modulate serotonin signalling in the ACC to reduce alcohol consumption opens up new possibilities for developing therapeutic strategies.
