A review of nonhuman primate models of early life stress and adolescent drug abuse

Abstract

Adolescence represents a developmental stage in which initiation of drug use typically occurs and is marked by dynamic neurobiological changes. These changes present a sensitive window during which perturbations to normative development lead to alterations in brain circuits critical for stress and emotional regulation as well as reward processing, potentially resulting in an increased susceptibility to psychopathologies. The occurrence of early life stress (ELS) is related to a greater risk for the development of substance use disorders (SUD) during adolescence. Studies using nonhuman primates (NHP) are ideally suited to examine how ELS may alter the development of neurobiological systems modulating the reinforcing effects of drugs, given their remarkable neurobiological, behavioral, and developmental homologies to humans. This review examines NHP models of ELS that have been used to characterize its effects on sensitivity to drug reinforcement, and proposes future directions using NHP models of ELS and drug abuse in an effort to develop more targeted intervention and prevention strategies for at risk clinical populations.

Keywords: Adolescence; Drug abuse; Monkeys; Self-administration; Sex; Stress.

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.)