Buspirone is a 5-HT1A receptor agonist, meaning it binds to and activates 5-HT1A receptors in the brain.

Initially, the 5-HT1A receptors are auto-inhibitory, so when buspirone activates them, it inhibits serotonin (5-HT) release from serotonergic neurons.

With prolonged use, the brain desensitizes these auto-inhibitory receptors and downregulates the 5-HT1A receptors, meaning they become less sensitive to the effects of serotonin.

This process leads to heightened excitation of serotonergic neurons, resulting in increased serotonin release over time.

This mechanism helps reduce anxiety and alleviate symptoms of generalized anxiety disorder (GAD). However, buspirone is not effective for phobias.

Review: Anxiety (Physiology 2)