The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors

Abstract

Stress is a complex experience that carries both aversive and motivating properties. Chronic stress causes an increase in the risk of depression, is well known to increase relapse of drug seeking behavior, and can adversely impact health. Several brain systems have been demonstrated to be critical in mediating the negative affect associated with stress, and recent evidence directly links the actions of the endogenous opioid neuropeptide dynorphin in modulating mood and increasing the rewarding effects of abused drugs. These results suggest that activation of the dynorphin/kappa opioid receptor (KOR) system is likely to play a major role in the pro-addictive effects of stress. This review explores the relationship between dynorphin and corticotropin-releasing factor (CRF) in the induction of dysphoria, the potentiation of drug seeking, and stress-induced reinstatement. We also provide an overview of the signal transduction events responsible for CRF and dynorphin/KOR-dependent behaviors. Understanding the recent work linking activation of CRF and dynorphin/KOR systems and their specific roles in brain stress systems and behavioral models of addiction provides novel insight to neuropeptide systems that regulate affective state.

Figure 1. Theoretical Framework of Activation of Dynorphin/KOR mediated Hedonic Processes before and after stress

The hedonic response (mood state) in a normal animal carries a total potential reward value Δm (for change in mood) after rewarding drug. The stressed animal has a larger Δm because the activation of dynorphin/KOR causes an increase in dysphoria, shifting the moods state negatively and thus increasing the amplitude of Δm. The reward (drug of abuse) now has as a larger potential positive valence so that the animal experiences more rewarding effects of the drug.