Stress effects on the neural substrates of motivated behavior

Abstract

Exposure to stress has profound, but complex, actions on motivated behavior and decision-making. These effects are central to core symptoms of a number of psychiatric disorders that are precipitated or augmented by stress, such as depressive disorders and substance use disorders. Studying the neural substrates of stress's effects on motivation has revealed that stress affects multiple targets on circuits throughout the brain using diverse molecular signaling processes. Moreover, stress does not have unitary effects on motivated behavior, but differences in the intensity, duration, intermittency, controllability and nature of the stressor produce qualitatively and quantitatively different behavioral endpoints. Unsurprisingly, the results of neuroscientific investigations into stress and motivation often open more questions than they resolve. Here we discuss contemporary results pertaining to the neural mechanisms by which stress alters motivation, identify points of contention and highlight integrative areas for continuing research into these multifaceted complexities.

Figure 1

Key studies referenced in this review. Select works discussed in this review include stress effects on motivated behaviors mediated by dopamine neurons in the VTA^–, their downstream targets in the NAc^–, and interactions with neuropeptides such as CRF^,, and BDNF^,, in each region. The second section includes discussion of stress effects on different forms of instrumental behavior and corresponding structural and functional alterations in corticostriatal circuitry supporting these behaviors^–, including regions such as the mPFC, OFC, dorsomedial striatum (DMS) and dorsolateral striatum (DLS).

Figure 2

Stress effects on effort-based decision-making. Acute restraint stress biases decision-making away from high-effort, high-reward options when a low-reward option is concurrently available for lower effort. The proposed mechanism for this effect is by reduction of reward-evoked dopamine release in the NAc as a result of release of CRF into the VTA during acute stress.