There are several pathophysiologic pathways through which prenatal exposure to cocaine may influence early brain development. The first major pathway involves the direct effects of cocaine on brain neurotransmitter systems. Because monoamine (MA) neurotransmitter receptors (NA, 5-HT and DA) are present early in corticogenesis, areas highly expressing these neurotransmitter systems may be especially susceptible to elevated synaptic MA levels secondary to cocaine’s main effect of blocking catecholamine reuptake at the presynaptic level3-5. In particular, as MA neurotransmitters play a key trophic role in brain development6, prenatal cocaine may alter normal mechanisms that modulate neuronal growth3. In the rabbit model, prenatal cocaine causes a functional uncoupling of the dopamine D1 receptor from its G-protein in cortical and subcortical areas, and associated cytoarchitectural alterations in excitatory pyramidal neurons and inhibitory interneurons7. Other cytoarchitectural alterations have been observed in mouse, rat and non-human primate models8-10. Additional less well understood mechanisms by which cocaine may directly impact early brain development include its interaction with other neurotransmitters, including GABA and glutamate11-13 and its effects on altering gene expression8, including dopaminergic and serotonergic systems14, 15, as well as multiple apoptosis-associated genes16.
