Functional deprivation of noradrenaline neurotransmission: effects of clonidine on brain development.

Publisher Summary The purpose of this chapter is to provide foundations for a working hypothesis on drug-induced functional neuroteratology. A class of centrally acting antihypertensive drugs, including clonidine, which are still being prescribed during pregnancy in humans, is used as the model. A hypothesis is put forward in this chapter which proposes that behavioral state-dependent changes in monoaminergic neuronal firing levels and patterns play a key role during early ontogeny in regulating neuron membrane potential, neurotransmitter release and neurotransmitter receptor sensitivity patterns in adulthood. Neurons show spontaneous activity that varies as a function of the behavioral state of the organism. This has been demonstrated for noradrenergic neurons of the locus coeruleus (LC), serotonergic neurons of the dorsal raphe (DR), dopaminergic neurons of the substantia nigra (SN) and cholinergic neurons of the dorsolateral part of the pons and basal forebrain. Because centrally acting antihypertensives predominantly affect the noradrenaline (NA) system in the brain, the induced modifications of central NA neurotransmission is also emphasized in this chapter.