Figure 1.

Localization of neurotransmitter circuits involved in the stress response and environmental toxicants that effect their function. The prefrontal cortex, amygdala, and hippocampus are the major nuclei of the limbic system that mediate the stress response through interactions with glucocorticoid and neuropeptides released centrally and peripherally. These interactions are further facilitated through dopaminergic projections (blue arrows) from the ventral tegmental area in the midbrain to the prefrontal cortex to assist with aspects of interpretation and memory of a stressful event. In addition, noradrenergic projections (green arrows) from the locus coeruleus in the brainstem to the hippocampus also participate in glutamate signaling and memory formation. An additional noradrenergic projection to the autonomic nervous system provides an important link between the peripheral and central mediators of the stress response. Signaling in the locus coeruleus is also regulated by corticotropin-releasing hormone (red arrow) sent from the paraventricular nucleus of the hypothalamus. Although simplified in this drawing, a complex reciprocal interaction (black arrows) between each of these anatomical regions provides additional regulation of the central stress response. Environmental toxicants have been shown to significantly impact the expression and function of specific neurotransmitter pathways in the stress circuit, with current research focused on the effects seen in the prefrontal cortex, hippocampus, and hypothalamus. Perturbations to neurotransmitter signaling can have severe consequences on multiple aspects of the stress circuit leading to maladaptive stress responses that may evolve into more serious neuropsychiatric disorders.