Fig. 1.

Schematic of the dynamic neurocircuitry and neurochemistry related to ELS and adolescent drug vulnerability. In response to a stressor, CRF (green line) is secreted from the hypothalamus (gray oval), triggering the release of adrenocorticotropic hormone (ACTH; dark gray line) from the anterior pituitary (gray oval), which initiates the release of cortisol (red line) from the adrenal gland (blue oval). ELS, however, results in a hyperactive HPA system whereby cortisol may show impaired negative feedback to the hypothalamus and anterior pituitary (both gray ovals), as well as extrahypothalamic structures, such as the PFC (purple oval; part of mesolimbic DA system) and the hippocampus (red oval) to shutdown secretion of cortisol. With increases in cortisol release, DA release may also increase in other areas of the mesolimbic system, such as the NAc, and directly affect the ability of drug reinforcers to stimulate DA release. Glutamate (orange line), as well as the GABAergic and serotonergic systems (not pictured) also serve as potent modulators of DA release throughout these major structures. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)