Insulin modulates emotional behavior through a serotonin-dependent mechanism

Area of Science:

• Neuroscience
• Metabolic Disorders
• Psychiatry

Background:

• Type-2 Diabetes (T2D) is linked to higher rates of major depressive disorder (MDD).
• Insulin resistance in T2D correlates with depression severity, but central insulin's role in MDD is unclear.

Purpose of the Study:

• To investigate if insulin modulates the serotonergic (5-HT) system to influence emotional behavior.
• To determine if insulin resistance in 5-HT neurons contributes to T2D-associated mood disorders.

Main Methods:

• Examined insulin's direct effects on dorsal raphe (DR) 5-HT neurons.
• Assessed the impact of intranasal insulin on anxiety-like behavior.
• Utilized high-fat diet-induced T2D animal models.

Main Results:

• Insulin directly inhibits DR 5-HT neuron activity, reducing 5-HT neurotransmission via 5-HT_1A receptors.
• Insulin-induced 5-HT neuromodulation is crucial for intranasal insulin's anxiolytic effects.
• Both the anxiolytic effect and neuronal response to insulin were diminished in T2D animals.

Conclusions:

• Insulin regulates emotional behavior by modulating DR 5-HT neurons and dampening 5-HT neurotransmission.
• Impaired insulin sensitivity in these neurons is critical for developing T2D-associated mood disorders.