The upside of stress: a mechanism for the positive motivational role of corticotropin releasing factor

Lemos, Julia C.; Alvarez, Veronica A.

doi:10.1038/s41386-019-0510-9

Cited by 10 publications

(9 citation statements)

References 8 publications

(10 reference statements)

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“…Our results suggest that CRF-containing neurons in either NAc shell or CeA can cause intense pursuit and increased consumption of cocaine through a positively-valenced motivational process, such as incentive salience or ‘wanting’ for drugs. This is similar to incentive roles of CRF-containing neurons in NAc and CeA that promote sucrose pursuit [ 14 , 16 , 19 ], and is compatible with suggestions that CRF system activation promotes over-eating of “comfort foods” primarily via positively-valenced processes that increase ‘wanting’ for those foods [ 55 ].…”

Section: Discussionsupporting

confidence: 80%

“…Incentive motivation roles of CRF-containing neurons may also help explain why vulnerability to relapse in addiction persists long after aversive withdrawal feelings and other life distresses subside [ 62 , 63 ]. Ultimately, the multiple motivational roles of CRF neural systems may be crucial to understanding the brain mechanisms underlying mood disorders as well as addictive relapse and substance abuse [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

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Corticotropin releasing factor (CRF) systems: Promoting cocaine pursuit without distress via incentive motivation

et al. 2022

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Corticotropin releasing factor (CRF) systems in limbic structures are posited to mediate stress-induced relapse in addiction, traditionally by generating distress states that spur drug consumption as attempts at hedonic self-medication. Yet evidence suggests that activating CRF-expressing neurons in the central amygdala (CeA) or nucleus accumbens (NAc) can magnify incentive motivation in absence of distress, at least for sucrose rewards. However, traditional CRF hypotheses in addiction neuroscience are primarily directed toward drug rewards. The question remains open whether CRF systems can similarly act via incentive motivation mechanisms to promote pursuit of drug rewards, such as cocaine. Here we tested whether optogenetic excitation of CRF-containing neurons in either NAc medial shell, lateral CeA, or dorsolateral BNST of transgenic Crh-Cre+ rats would spur preference and pursuit of a particular laser-paired cocaine reward over an alternative cocaine reward, and whether excitation served as a positively-valenced incentive itself, through laser self-stimulation tests. We report that excitation of CRF-containing neurons in either NAc or CeA recruited mesocorticolimbic circuitry to amplify incentive motivation to pursue the laser-paired cocaine: focusing preference on the laser-paired cocaine reward in a two-choice task, and spurred pursuit as doubled breakpoint in a progressive ratio task. Crucially indicating positive-valence, excitation of CRF neurons in NAc and CeA also was actively sought after by most rats in self-stimulation tasks. Conversely, CRF neuronal activation in BNST was never self-stimulated, but failed to enhance cocaine consumption. Collectively, we find that NAc and CeA CRF-containing neurons can amplify pursuit and consumption of cocaine by positively-valenced incentive mechanisms, without any aversive distress.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Corticotropin releasing factor (CRF) systems: Promoting cocaine pursuit without distress via incentive motivation

et al. 2022

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“…In contrast to most studies in the field focusing on motivation for palatable food, in our study, we avoided restricting rats’ access to food, which may create additional stress and, therefore, a different baseline. Here we show that acute exposure to natural stressors does not only dampen motivation as previously reported ( 8 , 9 , 11 ) but it can also invigorate work for primary rewards in a subset of individuals as it would be expected from the activating properties elicited by stress to facilitate survival ( 1 , 2 , 49 ). Acknowledging that acute stress exerts dichotomic effects in different individuals offers a more integrative view of the motivational impact of stress than the expectation of a homogeneous type of behavioral adaptation throughout the population.…”

Section: Discussionsupporting

confidence: 75%

“…Most reports to date have emphasized negative effects of acute stress in working for food rewards ( 8 , 9 , 11 ). Positive motivational qualities of acute stress have been barely recognized ( 7 ) and are much less understood ( 49 ). Most evidence on positive motivational effects of stress has been generated using pharmacological stressors and focusing on relapse to drugs of abuse ( 50 ) or on seeking for previously primed high-energy content food ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Opposite effects of stress on effortful motivation in high and low anxiety are mediated by CRHR1 in the VTA

et al. 2022

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Individuals frequently differ in their behavioral and cognitive responses to stress. However, whether motivation is differently affected by acute stress in different individuals remains to be established. By exploiting natural variation in trait anxiety in outbred Wistar rats, we show that acute stress facilitates effort-related motivation in low anxious animals, while dampening effort in high anxious ones. This model allowed us to address the mechanisms underlying acute stress–induced differences in motivated behavior. We show that CRHR1 expression levels in dopamine neurons of the ventral tegmental area (VTA)—a neuronal type implicated in the regulation of motivation—depend on animals’ anxiety, and these differences in CRHR1 expression levels explain the divergent effects of stress on both effortful behavior and the functioning of mesolimbic DA neurons. These findings highlight CRHR1 in VTA DA neurons—whose levels vary with individuals’ anxiety—as a switching mechanism determining whether acute stress facilitates or dampens motivation.

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“…The neuropeptide corticotropin releasing factor (CRF, also known as CRH) is widely known for its stress-induced activation of the hypothalamic-pituitary-adrenal axis, but CRF also acts in the brain to directly regulate both positive and negative motivated behavioral response to stressors (Lemos et al, 2012 ; Lemos and Alvarez, 2020 ; Baumgartner et al, 2021 ). Persistent CRF dysregulation following mild traumatic brain injury (mTBI) has been suggested to contribute to chronic psychiatric morbidities with abnormal stress-related neuronal responses and negative affective states associated with mTBI (Fox et al, 2016 ; Russell et al, 2018 ; Kosari-Nasab et al, 2019 ).…”

Section: Papers In This Collectionmentioning

confidence: 99%

Editorial: The synaptic basis of neuropathology

Nugent

Kirkwood

Lupica

et al. 2022

Front. Synaptic Neurosci.

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The upside of stress: a mechanism for the positive motivational role of corticotropin releasing factor

Cited by 10 publications

References 8 publications

Corticotropin releasing factor (CRF) systems: Promoting cocaine pursuit without distress via incentive motivation

Corticotropin releasing factor (CRF) systems: Promoting cocaine pursuit without distress via incentive motivation

Opposite effects of stress on effortful motivation in high and low anxiety are mediated by CRHR1 in the VTA

Editorial: The synaptic basis of neuropathology

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