Deep brain stimulation and fluoxetine exert different long-term changes in the serotonergic system

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Selective serotonin reuptake inhibitors (SSRIs) and ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) are known to modulate serotonergic activity.
• Understanding the distinct mechanisms by which these interventions impact the serotonergic system is crucial for therapeutic development.

Purpose of the Study:

• To compare the acute and long-term effects of vmPFC stimulation and fluoxetine on serotonin (5-HT) release and receptor expression in rats.
• To elucidate the differential mechanisms of action of fluoxetine and vmPFC DBS on the serotonergic system.

Main Methods:

• Rats were treated with either fluoxetine or subjected to vmPFC DBS for acute (1 day) and long-term (12 days) periods.
• Serotonin levels were measured in the hippocampus using microdialysis.
• Serotonin transporter (SERT), 5-HT_1A, and 5-HT_1B mRNA and receptor binding were assessed using in situ hybridization and autoradiography.

Main Results:

• Fluoxetine significantly increased extracellular serotonin levels acutely and long-term, while DBS showed a smaller acute increase without a sustained peak.
• Acute fluoxetine increased dorsal raphe SERT expression; acute DBS decreased it.
• Chronic fluoxetine decreased 5-HT_1A binding in the prefrontal cortex and hippocampus, whereas chronic DBS increased 5-HT_1B binding in several brain regions.

Conclusions:

• Both fluoxetine and vmPFC DBS modulate the serotonergic system, but through different mechanisms.
• Fluoxetine primarily affects serotonin transporter expression and receptor binding, while DBS influences receptor binding in a broader range of brain areas.