What do muscarinic M4 receptors do?

• A. Analgesia
• B. Analgesia and facilitate dopamine release
• C. Facilitate dopamine release
• D. No effect

Answer: (B)

Muscarinic M4 receptors are Gi/o-coupled receptors in the CNS that modulate neuronal activity in pain pathways and in striatal networks that control dopamine signaling. Activation of M4 receptors reduces cAMP and dampens excitability, which contributes to analgesic (antinociceptive) effects in pain pathways. At the same time, these receptors modulate dopaminergic transmission in striatal circuits, where their activation can alter dopamine release through complex network interactions involving cholinergic interneurons and GABAergic neurons. Because M4 receptor activity is linked to both analgesia and modulation of dopamine release, this combined effect best reflects their role, making the option describing analgesia and facilitation of dopamine release the most accurate.