Neurochemical teratology: 5-hydroxyindole concentrations in discrete areas of rat brain after the pre- and neonatal administration of phencyclidine and imipramine

Abstract

The administration of drugs affecting 5-hydroxytryptamine to pregnant rats has been shown to disturb the activity and the emotionality of the offspring (1). Clinical studies suggest that 5-hydroxyindole metabolism may be abnormal in certain types of affective disorders (2), but the experimental investigation of the relationship between brain monoamines and behaviour is complicated by the lack of satisfactory animal models. Monoamine concentrations can be altered by the acute use of drugs or by selective lesions, but in both cases the results of subsequent behavioural and neurochemical studies may be influenced by a lack of specificity inherent in the techniques. Since the behavioural consequence of prenatal drug administration appear to be permanent (1), it was of interest to investigate 5-hydroxyindole concentrations in discrete areas from the brain of the offspring of rats treated with two drugs known to affect the metabolism of phenocyclidine in mature rats affects both the concentration and the release of 5-hydroxytryptamine (3): imipramine affects the neuronal re-uptake of 5-hydroxytryptamine. Since the primary aim of the experiments was to see whether permanent changes in 5-hydroxyindole concentrations could be induced, and not how or when, phencyclidine and imipramine were administered throughout pregnancy and the suckling period.