ReviewThe mesoaccumbens dopamine in coping with stress
Highlights
► Fluctuations of tonic dopamine levels characterize the mesoaccumbens stress response. ► High tonic dopamine in accumbens supports active coping whereas low tonic DA is associated with passive coping. ► In novel stressful situations the balance between cortical dopamine and norepinephrine controls tonic dopamine in accumbens. ► Individual variability in coping styles is associated with opposite mesoaccumbens dopamine stress responses.
Introduction
Evidence for a stress response by the mesoaccumbens dopamine (DA) system is compelling. Stress-induced changes in DA metabolism within the nucleus accumbens (NAc) were first reported in the late seventies (Fadda et al., 1978) and eighties (Robinson and Becker, 1986, Dunn and Berridge, 1987, Antelman et al., 1988, Cabib et al., 1988, Kalivas and Duffy, 1989). Data collected using intracerebral microdialysis and voltammetry in vivo confirmed the view that stressors modulate DA release in the NAc (Abercrombie et al., 1989, Imperato et al., 1991, Puglisi-Allegra et al., 1991, Doherty and Gratton, 1992, Rossetti et al., 1993, Pothos et al., 1995). Finally, DA transmission in NAc has been shown to modulate the behavioral responses to stress (Rossetti et al., 1993, Ventura et al., 2002, Scornaiencki et al., 2009).
The brain is the key organ of stress reactivity, coping, and recovery processes and brain mechanisms involved in the stress response are responsible for the outcomes of stressful life events in terms of resilience or pathology (Mancini and Bonanno, 2006, Rutter, 2006, Krishnan et al., 2007, Taylor and Stanton, 2007, Feder et al., 2009, Ganzel et al., 2010, McEwen and Gianaros, 2010). Altered NAc DA transmission has been consistently implicated in psychopathology (Lipska, 2004, Everitt et al., 2008, Goto and Grace, 2008, Robinson and Berridge, 2008, Carlezon and Thomas, 2009, Floresco et al., 2009, O'Sullivan et al., 2009). Therefore, mesoaccumbens DA is likely to be a major mediator of the stress outcomes.
Despite these considerations, the role of the mesoaccumbens DA response in stress has been generally neglected in the debate on the role of NAc DA and in the literature on the brain mechanisms involved in stress response. This could be because of the strong association between mesoaccumbens DA, reward and seeking that seemed at odds with its involvement in stress reactions normally involving aversion and avoidance. Another obstacle in identifying a role for mesoaccumbens DA in stress response is the direction of changes in NAc DA release observed in animals exposed to stress. In fact, although most studies report enhanced DA release (Horvitz, 2002, for review), some report stress-induced inhibition of DA (Puglisi-Allegra et al., 1991, Rossetti et al., 1993, Cabib and Puglisi-Allegra, 1994, Pothos et al., 1995, Rada et al., 1998, Mangiavacchi et al., 2001, Ventura et al., 2001, Ventura et al., 2002, Pascucci et al., 2007).
In this review we propose that fluctuations of tonic levels of DA within the NAc have a role in sustaining different coping strategies in stressful situations. The first section of the review is dedicated to discussing differences between stressors and stimuli endowed with negative hedonic value in theoretical terms and in terms of the response they can elicit in DA neurons. In the second section we review data on the dynamics of DA outflow in the NAc of experimental animals exposed to stressful experiences. These dynamics will be evaluated in relation to the behavioral responses expressed by the stressed organisms. In the third part we describe the brain mechanisms that regulate fluctuations of DA in NAc during experiences with a novel, unavoidable/uncontrollable stressor. In the final part of the review we will present our hypothesis based on the reviewed data, the general concepts of coping and appraisal, and recently proposed roles of mesoaccumbens DA.
Section snippets
Stress, stressors and stress responses
Historically, research on stress and stress-associated phenomena has been hindered by ambiguous definitions. Indeed, the term stress has been used to indicate both a response (or a set of responses) and the stimuli that promote the response (Huether et al., 1999, Ursin and Eriksen, 2004). To avoid confusion, in the present review we explicitly refer to “stress responses” and use the terms “stressors” or stressful stimuli, conditions, situations and events to indicate whatever promotes the
Changes in NAc DA release in the course of stressful experiences
Interpretation of results reported by studies on NAc DA stress responses is complicated by differences in procedures, protocols and methods used. In fact, samples used for neurochemical assays are collected at different time points from the beginning, or the end, of experiences that can last from seconds to hours, be novel, repeated or chronic and promoted by conditioned or unconditioned aversive stimuli. Therefore, these results need to be carefully evaluated in the light of the concepts and
Enhanced DA release
Novel stressful experiences enhance DA release in the NAc through activation of prefrontal cortical alpha-1 adrenergic receptors by high levels of released norepinephrine (NE) (Nicniocaill and Gratton, 2007, Pascucci et al., 2007). Indeed, the experience with a novel stressor promotes a rapid, massive and transient increase in NE release within the medial pre-frontal cortex (mpFC) which parallels the enhancement of mesoaccumbens DA release (Pascucci et al., 2007). A selective depletion of
Coping with stress
As discussed in the first section of this review, coping is the necessary outcome of any stressful situation because the organism cannot sustain the stress responses. Indeed, converging evidences from psychological and ecological studies strongly support the view that coping adopted to deal with stressful conditions is the major determinant of stress resilience (Rutter, 2006, Koolhaas et al., 2007, Taylor and Stanton, 2007, Feder et al., 2009;). Coping strategies seek to manage, master, reduce,
General conclusions
We have reviewed evidence supporting the hypothesis that large fluctuations of tonic levels of DA in the NAc play a major role in coping with events appraised as stressful. In particular, we have suggested that high levels of tonic DA support expression of costly and risky defensive responses which characterize active coping strategies, whereas reduced levels of tonic DA block these responses. As discussed, each coping strategy is effective in specific conditions. Indeed, active coping
Acknowledgements
The authors wish to thank Prof. A. Mele and Dr. E. De Leonibus for the helpful suggestions. The authors were supported by “Sapienza” Università di Roma, Italy.
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