Which mechanism explains prolactin elevation associated with certain antipsychotics?

• A. Serotonin reuptake inhibition in the raphe nuclei
• B. D2 blockade in the tuberoinfundibular pathway
• C. NMDA receptor antagonism in the cortex
• D. D1 receptor blockade in the nigrostriatal pathway

Answer: (B)

Dopamine normally keeps prolactin release in check by acting on D2 receptors on pituitary lactotrophs in the tuberoinfundibular pathway. When an antipsychotic strongly blocks those D2 receptors in this pathway, the inhibitory signal is lost, and prolactin secretion increases. This is the mechanism behind antipsychotic-induced hyperprolactinemia, and it explains why drugs with potent D2 blockade in the pituitary tend to raise prolactin levels. Other options don’t fit because they involve different systems: serotonin-related mechanisms can affect prolactin in other contexts but aren’t the primary cause here; NMDA antagonism affects cognition; and D1 blockade in the nigrostriatal pathway is linked to movement symptoms, not prolactin regulation.