Prenatal amphetamine effects on behavior: possible mediation by brain monoamines.

The present analysis indicates that the literature is currently too limited to draw anything but very tentative conclusions about whether amphetamine during pregnancy is detrimental to the offspring. However, exposure to very high doses of the drug appears to be teratogenic; and studies in which animals were exposed to lower doses of either amphetamine or methamphetamine throughout pregnancy indicate that this class of drugs can have long-term neurochemical and behavioral consequences for rodent offspring. The commonly reported behavioral effects include abnormal responding on aversively motivated tasks, and heightened motor activity which might be associated with slower habituation. Neurochemical studies have focused on various aspects of the monoamine neurotransmitter systems and suggest that prenatal amphetamine exposure can increase the synthesis and turnover of DA and NE and reduce the number of adrenergic receptors in adult offspring. In addition, concentrations of NE appear to be reduced at birth suggesting prenatal depletion and are sometimes found to be altered at later times. Although these studies are provocative, the absence of pair-fed controls and cross-fostering prevent ruling out the possible confounding effects of undernutrition and altered maternal care. In addition to the above limited empirical support, the effects of amphetamines on adult brain provide a logical rationale for anticipating that prenatal exposure to the drug could be detrimental. This rationale is essentially that amphetamine can have long-term effects of monoaminergic systems in the brains of adults, including neural degeneration; and, since the drug can cross the placenta, it should also have long-lasting consequences for the developing fetus. It is proposed that the later stages of gestation might be particularly sensitive to the long-term behavioral effects of amphetamine. Although there are no systematic studies on critical periods for the effects of prenatal amphetamine exposure, several reports indicate that exposure restricted to GD 12-15 has little effect. Since amphetamine predominantly affects the neuron terminals and terminals develop later than GD 15, it is proposed that amphetamine exposure later in gestation, after the monoaminergic systems are more mature, will have a greater effect. The rationale for the long-term behavioral effects of prenatal amphetamine is based on studies indicating that 1) rapidly developing systems are very sensitive to insult from external agents; 2) the monoaminergic systems and pituitary-adrenal organization are developing rapidly during the later gestation and early neonatal periods; 3) amphetamine influences each of these systems in adults and the monoamine systems in fetuses; and, 4) alterations in the systems cause predictable behavioral changes.(ABSTRACT TRUNCATED AT 400 WORDS)