**5.1 Central Co-localization of nicotinic and muscarinic receptors**

The overlapping distributions of nAChRs and mAChRs in the brain is well characterized. Up to 90% of central cholinergic neurons express both types of receptors as seen in several thalamic nuclei, the interpeduncular nucleus, the superior colliculus, and the cerebral cortex. These overlaps signify important interactions. For example, in striatal DA system, nAChRs and mAChRs counteract each other's effects, in that DA efflux is stimulated by nAChRs activation or in contrast, by inhibition of mAChRs [18]. Similarly, in corpus striatum, ACh released from cholinergic interneurons can activate α4β2 nAChRs mediating release of GABA. This evoked release, on the other hand, can be negatively modulated by M4 mAChRs co-expressed on the same GABAergic terminals [19]. Therefore, it appears that some of the counteractive effects of nAChRs and mAChRs observed in peripheral organs (described above, see 4.2) also extend to the brain. However, exploitation of such interactions is yet to be fully explored.
