Effect of central nervous system acting drugs on brain cell replication in vitro

The role in the regulation of cell replication of the neurotransmitter compounds and the drugs which affect their balance was studied in vitro, using morphologically preserved brain slices. Compounds affecting noradrenergic, dopaminergic and serotoninergic neurotransmitter systems reduced the brain cell replication, measured in terms of the rate of [3H]thymidine incorporation into DNA. The reduction was dose dependent and half-maximal effects were obtained at about 1-5 x 10(-4) M concentrations. Although agonists and antagonists both showed similar inhibitory effect, the action of agonists was reversed by the appropriate antagonists. Also, the pharmacologically active isomers were several-fold more effective than the inactive isomers in forebrain slices, although with cerebellar slices the selectivity was less marked. Cyclic nucleotides and drugs affecting cholinergic neurotransmitter systems were apparently ineffective. These results indicate that monoamines may be involved in the regulation of cell replication in the developing brain. Furthermore, as some of the CNS acting drugs tested are suspected behavioural teratogens the present results suggest that the reported behavioural abnormalities in the offspring may be related, in part, to a chronologically determined interference with the formation of certain cell types.