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The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal - PubMed

Review

. 2020 Jul;52(1):2429-2465.

doi: 10.1111/ejn.14714. Epub 2020 Apr 20.

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Review

The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal

Jennifer A Ross et al. Eur J Neurosci. 2020 Jul.

Abstract

Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one hand, the dopaminergic mesocorticolimbic system evaluates the rewarding or reinforcing potential of a stimulus, while on the other, the noradrenergic stress response system evaluates the risk of threat, commanding attention, and engaging emotional and physical behavioral responses. Sex-specific patterns in the anatomy and function of the arousal system suggest that sexually divergent therapeutic approaches may be advantageous for neurological disorders involving arousal, learning, and memory. From the lens of the triple network model of psychopathology, we argue that post-traumatic stress disorder and opiate substance use disorder arise from maladaptive learning responses that are perpetuated by hyperarousal of the salience network. We present evidence that catecholamine-modulated learning and stress-responsive circuitry exerts substantial influence over the salience network and its dysfunction in stress-related psychiatric disorders, and between the sexes. We discuss the therapeutic potential of targeting the endogenous cannabinoid system; a ubiquitous neuromodulator that influences learning, memory, and responsivity to stress by influencing catecholamine, excitatory, and inhibitory synaptic transmission. Relevant preclinical data in male and female rodents are integrated with clinical data in men and women in an effort to understand how ideal treatment modalities between the sexes may be different.

Keywords: catecholamines; endocannabinoid; locus coeruleus; opiate use disorder; opiate withdrawal; post-traumatic stress disorder; sex-specific patterns; stress.

© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no competing financial interests to disclose.

Figures

FIGURE 1
FIGURE 1

The endocannabinoid and catecholamine systems converge on the prefrontal cortex, hippocampus and amygdala, which are anatomical substrates of stress, learning, and memory processes. The catecholamine modulators norepinephrine (NE) and dopamine (DA) are released from the locus coeruleus (LC) and ventral tegmental area (VTA), respectively. NE and DA are key players in conveying the emotional valence of a stimulus, thereby influencing learning and memory processes. These processes are fundamentally supported by glutamatergic and GABAergic signaling. The endocannabinoid system further refines catecholamine modulation of stress, learning, and memory on a global level as it is ubiquitously present, active in multiple stress-responsive regions, and can influence learning and memory. This may be particularly relevant for PTSD, as the specific alterations induced by the cannabinoid system may facilitate the extinction of the high emotionally valenced memories that drive the disorder

FIGURE 2
FIGURE 2

Sex Differences in catecholamine neurocircuitry involved in learning and memory and stress responses. Sexual dimorphisms are depicted in critical brain regions for stress, learning, and memory and the catecholamine neurotransmitters that modulate them. Further understanding of how these sex differences can potentially influence the etiology and progression of many psychiatric disorders and inform therapeutic approaches

FIGURE 3
FIGURE 3

The endocannabinoid (eCB) system may be uniquely positioned to modify cellular adaptations to stress in the LC, particularly those involved with opioid withdrawal. The eCB system may be positioned to mitigate increased CRF release onto LC via amygdalar afferents during opioid withdrawal (Figure 3, panel 1). Broadly, this notion is supported by evidence that increasing cannabinoid tone in amygdala restrains HPA axis activity and CRF release, thereby restraining excitatory input onto LC neurons (Figure 3, panel 2). In the LC, CB1r is expressed post-synaptically on LC-NE neurons as well as presynaptically including on glutamate terminals (Panel 3A). Panel 3 depicts CB1r localized pre- and post-synaptically in the LC, potentially in a position to abrogate the increased excitability of the LC driven by the increased tone of GLU from LC afferents during withdrawal (Panel 3B)

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References

    1. Adinoff B (2004). Neurobiologic processes in drug reward and addiction. Harvard Review of Psychiatry, 12(6), 305–320. 10.1080/10673220490910844 - DOI - PMC - PubMed
    1. Aghajanian GK (1978). Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature, 276(5684), 186–188. - PubMed
    1. Aghajanian GK, Kogan JH, & Moghaddam B (1994). Opiate withdrawal increases glutamate and aspartate efflux in the locus coeruleus: An in vivo microdialysis study. Brain Research, 636(1), 126–130. - PubMed
    1. Akaoka H, & Aston-Jones G (1991). Opiate withdrawal-induced hyperactivity of locus coeruleus neurons is substantially mediated by augmented excitatory amino acid input. The Journal of Neuroscience, 11(12), 3830–3839. - PMC - PubMed
    1. Akiki T, Averill C, & Abdallah C (2017). A network-based neurobiological model of PTSD: Evidence from structural and functional neuroimaging studies. Current Psychiatry Reports, 19, 81. 10.1007/s11920-017-0840-4 - DOI - PMC - PubMed

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