Muscarinic receptor blockade increases basal acetylcholine release from striatal slices

The main objective of these studies was to determine whether the basal release of acetylcholine (ACh) from brain slices was subject to modulation by muscarinic receptor blockade. Incubation of striatal slices with the muscarinic antagonist atropine increased ACh release in a concentration-dependent manner with a maximal effect (1.4-1.8 times control release) achieved with 0.1 to 1.0 microM. In contrast, ACh release from hippocampal slices was unaltered by any concentration of atropine tested, indicating that the basal release of neurotransmitter from striatum, but not hippocampus, was subject to modulation by muscarinic receptor blockade. Incubation of striatal slices with 1 microM tetrodotoxin or removal of Ca++ from the medium decreased the basal release of ACh by 20% and abolished the atropine-induced release of ACh; neurotransmitter release from hippocampal slices was unaltered by tetrodotoxin. Thus, part of the basal release of ACh from striatal slices is a consequence of the intrinsic impulse activity of cholinergic neurons and it is this component of release that is atropine-sensitive. Oxotremorine was unable to antagonize the atropine-induced release of ACh, even with concentrations 100 times that of atropine, whereas pirenzepine increased ACh release and, like that of atropine, the effect of pirenzepine was sensitive to tetrodotoxin and resistant to oxotremorine. These results indicate that a component of basal ACh release from striatal slices is subject to modulation by a receptor that is sensitive to atropine and pirenzepine, but not to oxotremorine, suggesting that this site differs from the nerve terminal muscarinic autoreceptor.