In vitro and in vivo inhibition by lithium of enkephalin binding to opiate receptors in rat brain.

The in vitro and in vivo effects of lithium ions on opiate receptor binding were studied in the cerebral cortex, the hippocampus and the basal ganglia of the rat. In vitro, lithium ions inhibited enkephalin binding to opiate receptors through a reduction in the number of binding sites, whereas the affinity was unchanged or only slightly decreased. In vivo, long term ingestion of lithium (3 weeks), during which the rats were maintained at a serum lithium level of approximately 1 mM, also inhibited enkephalin binding to rat neuronal membranes (P2-fractions) through a reduction of the number of opiate receptor binding sites, whereas the affinity was unchanged. No lithium could be detected in the suspension of neuronal membranes from the lithium-treated rats, and no difference in the concentration of endogenous opioid peptides was found between control rats and lithium-treated rats. The opiate receptors from control rats and lithium-treated rats did no display any difference in lithium sensitivity. This data suggest that administration of lithium to rats in small doses reduces opiate receptor binding of enkephalin.