Effects of lithium on [3H](-)quinuclidinyl benzilate [( 3H](-)QNB) binding to rat brain muscarinic cholinergic receptors

Addition of lithium in vitro inhibited the binding of [3H](-)QNB to muscarinic cholinergic receptors of homogenates of tissue prepared from the striatum, cortex, and hippocampus of rat brain. Chronic in vivo exposure of rats to lithium in their food produced serum levels of lithium comparable to therapeutic levels. After in vivo exposure, the tissue homogenates prepared from these rats had an apparent decrease in receptor density in the three brain areas. However, if the tissue homogenates were washed twice, before addition to the assays, no differences in binding were detectable. Similar effects on unwashed and washed tissue homogenates can be demonstrated after in vivo exposure to lithium. Therefore, the apparent decrease in binding after in vivo lithium treatment is probably due to lithium retained in the tissue. No permanent alterations in the muscarinic receptor characteristics were measurable after the removal of the lithium. Nevertheless, in vivo interactions at muscarinic receptors may be important under conditions when therapeutic levels of lithium are present.