Behavioural retardation in the neuropathology of mental retardation.

A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviours in the laboratory in order to derive animal models of behavioural retardation. Rat dams were administered either methylazoxymethanol, metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams were studied on the behavioural tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-OHDA (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adult. The behavioural battery that the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviours, and a parameter under which diverse behaviours were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spacial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphetamine induced activity. It was shown that prenatal methylazoxymethanol, metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride, altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d-amphetamine induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded on the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85% depletion compared to control values) caused notable impairments. These diverse findings seem to implicate dopaminergic processes in brain development.