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Patel AJ, Barochovsky O, Lewis PD. 
“Psychotropic Drugs And Brain Development: Effects On Cell Replication In Vivo And In Vitro”. 
Neurophrmacology. 1981;20(12B):1243-1249.
Effects of certain psychotropic drugs, which are suspected behavioural teratogens, on cell replication in the developing brain were investigated using both biochemical and morphological techniques. Reserpine (a monoamine depletor) chlorpromazine, thioridazine and haloperidol (which mainly acts on postsynaptic receptors as a dopamine antagonist), and lysergic acid diethylamide {believed to affect serotonin systems)-resulted in a severe reduction of cell replication, measured in terms of the ingrate of [3H]thymidine incorporation into brain DNA of I l-day old rats. In the forebrain the rate of DNA labelling was about one third to one half of controls during the period 4-30, 14-30, 10-24 and 1-2 hr after subcutaneous administration of rcserpine (2.5 mg/kg), chlorpromazine (50 mg/kg), haloperidol (20 mg/kg) and lysergic acid diethylamide (1 mg/kg) respectively. The depression was dose dependent and the half maximal effect was produced with approx. 0.15 mg/kg reserpine, 10 mg/kg chlorpromazine, 15 mg/kg, thioridazine, 7 mg/kg, haloperidol and 0.5 mg/kg lysergic acid diethylamide. The effect on the cerebellum was similar but less marked. Parallel histological studies showed that in both reserpine- and chlorpromazine-treated rats the turnover time of cell replication was markedly increased in the forebrain subependymal layer, while in the cerebellar external granular layer there was a decrease in-the mitotic index and an increase in the degeneration of post-mitotic cells. The role of the drugs' effecting neurotransmitter balance in the regulation of cell replication was also studied in vivo using morphologically preservedbrain slices. The drugs affecting monoamine neurotransmitter systems reduced the rate of DNA labelling in a dose-dependent manner. Agonist and antagonists both showed similar inhibition and the half-maximal effect was obtained with approx. 104M concentrations. The drugs affecting cholinergie systems were apparently ineffective. The results of both in vivo and in vitro experiments suggest that the claimed behavioural teratogenic action of the psychotropic drugs tested may be related, in parts to a chronologieally-determined interference with the formation of certain cell types.
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