Kinetics of the uptake of monoamines into synaptosomes from rat brain. Consequences of lithium treatment and withdrawal.

The uptake systems for noradrenaline (NA) and 5-hydroxytryptamine (5-HT) into synaptosomal preparations from rat brain were found to consist of two components, a low-capacity and a high-capacity process. Administration of lithium (2 mequiv./kg) for 12 days was found to cause an increase in the activity of the low-capacity uptake process for NA, but to markedly inhibit the high-capacity system for this neurotransmitter. Following withdrawal of lithium, the activity of the low-capacity system returned to control values, but there was a profound enhancement of the high-capacity uptake process of NA. Both the low- and the high-capacity uptake systems for 5-HT were found to be inhibited by the administration of lithium. The reduced activity of the high-capacity system resulting from administration of lithium was still present 2 days after the cessation of treatment with the drug, whereas the low-capacity process was found to be further depressed. The uptake of dopamine (DA) into synaptosomal preparations appeared to be more complex than that of NA and 5-HT, since the shape of the substrate-velocity curve implied some form of multiple and co-operative process. The administration of lithium resulted in an enhancement of the uptake of DA in all regions of the brain examined, while 2 days of withdrawal from the drug caused a reduction to below control values in the amount of DA taken up. It therefore seems that alterations in monoaminergic uptake processes play a part in the mode of action of lithium, and may be involved in the genesis of the lithium-withdrawal phenomenon.