Functional changes implicating dopaminergic systems following perinatal treatments

Abstract

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 behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-hydroxydopamine (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 adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial 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 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 according to 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. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered.