Muscarinic Receptor Subtypes in the Central Nervous System

This chapter discusses the muscarinic receptor, found primarily in the CNS and nonskeletal muscle. In addition to interneurons in, for example, the caudate nucleus and the cerebral cortex, there are a number of known cholinergic pathways in the brain. These include the septohippocampal pathway as well as those from the nucleus basalis of Meynert to the frontal cortex and the pathway coursing through the habenula en route to the interpeduncular nucleus–ventral tegmental area. The experimental findings suggest that muscarinic receptors are heterogeneous. Both agonists and antagonists distinguish among different subclasses of the receptor based on affinity. Whether these subtypes are distinct entities, each linked to separate effector systems, or represent different functional or conformational states of the same receptor is the central issue. The evidence for multiple muscarinic receptors and their regulation is discussed in the chapter. Muscarinic receptors are ubiquitous in the brain, in terms of receptor density and of their involvement in behavioral phenomena. Studies of the binding of radioligands to homogenized tissue, together with autoradiographic analyses of brain sections, provide detailed maps of muscarinic receptor distribution throughout the brain.