Interactions of drugs and electroshock treatment on cerebral monoaminergic systems

The interaction of EST and drugs on the CSF levels of several monoamine metabolites was studied with four drugs that have been used in the treatment of psychiatric disorders, namely, lithium, carbamazepine, imipramine, and haloperidol. EST-drug interactions were observed with each of these drugs on one or more monoaminergic systems. All interactions were antagonistic in nature. Changes in the CSF levels of monoamine metabolites did not always reflect corresponding changes in the monoamine turnover; the increase in 5HIAA seen after chronic Li was due to slower removal of this metabolite from the CSF. However, the changes in the CSF levels of DA and 5HT metabolites following chronic HLDL reflected changes in the turnover of the parent amine in the brain. The effects of both HLDL and EST on DA metabolism in the intact brain could be related to alterations by these treatments of the responsiveness of DA presynaptic receptors. Similarly, the effect of HLDL on 5HT turnover and the antagonistic interaction of EST on this HLDL-induced effect were associated with changes in 3H-IMI binding sites that label the 5HT transporter in serotonergic presynaptic terminals. The results are discussed with the aid of a model that depicts possible relationships between pre- and postsynaptic variables and their influence on each other. According to this model an increase in the neurotransmitter turnover is associated with "down regulation" of both pre- and postsynaptic receptors whereas a decrease in turnover is associated with receptor "up regulation." However, "up regulation" of receptors is not necessarily associated with augmented postsynaptic response. Analysis of the model variables by the "binding equation" which obeys the Clark occupancy principle revealed that receptor "up regulation" which is associated with decreased turnover may result in either an augmented or a depressed postsynaptic response (related to the number of occupied receptors). The direction of the response depends on the ratio between the rate of receptor "up regulation" and the rate of decrease in neurotransmitter turnover.