Stronger mGlu5 signaling in excitatory brain cells may speed up antidepressant effects through AMPA receptor activation

Intravenous injection of TAT-Homer1a elicits rapid antidepressant effects.

• Mimicking Homer1a upregulation is associated with fast-acting antidepressant effects.
• TAT-Homer1a enhances mGlu5 signaling, which may increase mTOR pathway activity.
• This treatment upregulates synaptic AMPA receptor expression and activity.
• The antidepressant effects depend on mGlu5 activation in specific excitatory neurons.
• TAT-fused peptides that modulate mGlu5 and AMPA receptor activity could represent a novel approach for antidepressant treatment.

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