Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress

Polter, Abigail M.; Barcomb, Kelsey; Chen, Rudy W; Dingess, Paige M.; Graziane, Nicholas; Brown, Travis E.; Kauer, Julie A.

doi:10.7554/elife.23785

Cited by 40 publications

(29 citation statements)

References 84 publications

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“…Given the role of dynorphin/KOR interactions in modulating activity of both dopaminergic and nondopaminergic neurons in VTA (Polter et al, ), quantification of KOR in VTA in humans would be of significant interest. However, VTA quantification is challenging with [ 11 C]GR103545 given the small volume of this structure and the low PET signal observed in this region.…”

Section: Discussionmentioning

confidence: 99%

Kappa opioid receptor binding in major depression: A pilot study

Miller

Zanderigo

Purushothaman

et al. 2018

Synapse

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Endogenous kappa opioids mediate pathological responses to stress in animal models. However, the relationship of the kappa opioid receptor (KOR) to life stress and to psychopathology in humans is not well described. This pilot study sought, for the first time, to quantify KOR in major depressive disorder (MDD) in vivo in humans using positron emission tomography (PET). KOR binding was quantified in vivo by PET imaging with the [ C]GR103545 radiotracer in 13 healthy volunteers and 10 participants with current MDD. We examined the relationship between regional [ C]GR103545 total volume of distribution (V ) and diagnosis, childhood trauma, recent life stress, and, in a subsample, salivary cortisol levels during a modified Trier Social Stress Test (mTSST), amygdala, hippocampus, ventral striatum and raphe nuclei. Whole-brain voxel-wise analyses were also performed. [ C]GR103545 V did not differ significantly between MDD participants and healthy volunteers in the four a priori ROIs (p = 0.50). [ C]GR103545 V was unrelated to reported childhood adversity (p = 0.17) or recent life stress (p = 0.56). A trend-level inverse correlation was observed between [ C]GR103545 V and cortisol area-under-the curve with respect to ground during the mTSST (p = 0.081). No whole-brain voxel-wise contrasts were significant. Regional [ C]GR103545 V , a measure of in vivo KOR binding, does not differentiate MDD from healthy volunteers in this pilot sample. Future studies may examine KOR binding in subgroups of depressed individuals at increased risk for KOR abnormalities, including co-occurring mood and substance use disorders, as well as depression with psychotic features.

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Section: Discussionmentioning

confidence: 99%

Kappa opioid receptor binding in major depression: A pilot study

Miller

Zanderigo

Purushothaman

et al. 2018

Synapse

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“…It was speculated that this might improve an active coping and enhance a "flight or fight" response (Müller and Schumann, 2011a). Stress modifies the function of the mesolimbic DA system Kreibich et al, 2009) and its excitatory (Garcia-Keller et al, 2016) and inhibitory inputs (McLaughlin et al, 2003;Polter et al, 2017), in a way to cross-sensitize the system to subsequent psychostimulant behavioral effects and to their self-administration propensity (Cruz et al, 2011;. A single episode of social defeat stress can increase the mesocorticolimbic expression of the immediate early gene cFos, which is an indicator of neuronal activation Cooper et al, 2017).…”

Section: Facilitated Recovery and Coping With Psychological Stressmentioning

confidence: 99%

“…However, the same studies showed that days later an augmented effect emerges, which suggests that potential acute instrumentalization effects of the drug revert after a short time and render the organism in a drug-sensitized state that actually facilitates addiction-development . In the brain, µ-and -opioid receptor signaling and its activation by endogenous enkephalin and dynorphin, respectively, was enhanced after stress (McLaughlin et al, 2003;Nikulina et al, 2008;Polter et al, 2017).…”

Section: Facilitated Recovery and Coping With Psychological Stressmentioning

confidence: 99%

Non-pharmacological factors that determine drug use and addiction

Ahmed

Badiani

Miczek

et al. 2020

Neuroscience & Biobehavioral Reviews

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Based on their pharmacological properties, psychoactive drugs are supposed to take control of the natural reward system to finally drive compulsory drug seeking and consumption. However, psychoactive drugs are not used in an arbitrary way as pure pharmacological reinforcement would suggest, but rather in a highly specific manner depending on non-pharmacological factors. While pharmacological effects of psychoactive drugs are well studied, neurobiological mechanisms of non-pharmacological factors are less well understood. Here we review the emerging neurobiological mechanisms beyond pharmacological reinforcement which determine drug effects and use frequency. Important progress was made on the understanding of how the character of an environment and social stress determine drug self-administration. This is expanded by new evidence on how behavioral alternatives and opportunities for drug instrumentalization generate different patterns of drug choice. Emerging evidence suggests that the neurobiology of non-pharmacological factors strongly determines pharmacological and behavioral drug action and may, thus, give rise for an expanded system's approach of psychoactive drug use and addiction.

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“…Additionally, stress is reported to augment addictive behaviors via an increase in the rewarding properties or rewarding memory of cocaine (McLaughlin et al, 2003;Kreibich et al, 2009;Schindler et al, 2010Schindler et al, , 2012Montagud-Romero et al, 2015). These modulations of addictive behaviors are attributed to stress-and aversive stimulus-induced neuroadaptation and the release of stress-related neurotransmitters and neuromodulators, such as corticotropin-releasing factor (CRF), the j-opioid agonist dynorphin, and noradrenaline (NA), in reward-related circuitry (Shaham & Hope, 2005;Smith & Aston-Jones, 2008;Ungless et al, 2010;Wise & Morales, 2010;Graziane et al, 2013;McReynolds et al, 2014;Polter & Kauer, 2014;Mantsch et al, 2016;Stelly et al, 2016;Polter et al, 2017). Moreover, studies have revealed that the effects of neurotransmitters and neuromodulators on information processing are altered following cocaine administration.…”

Section: Involvement Of Ldt Plasticity In Stress-related Behaviorsmentioning

confidence: 99%

Neuroplasticity in cholinergic neurons of the laterodorsal tegmental nucleus contributes to the development of cocaine addiction

Kaneda

2018

Eur J of Neuroscience

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The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus that sends cholinergic, glutamatergic, and gamma-aminobutyric acid (GABA)-ergic projections to the ventral tegmental area (VTA), a key brain region associated with reward information processing and reinforcement learning, and thus, with addiction induced by drugs of abuse, including cocaine. Recent studies have revealed that the LDT, in addition to the VTA, plays important roles in the development and expression of cocaine-induced addiction and stress-induced enhancement of addictive behaviors. Additionally, neuroplasticity induced in LDT cholinergic neurons by repeated cocaine administration critically contributes to these behaviors. Elucidation of the underlying mechanisms of cocaine-induced neuroplasticity in the LDT that influences reward circuit activity may lead to the development of therapeutic strategies to treat cocaine addiction and stress-induced reinstatement of cocaine use. This review summarizes recent progress in the study of the LDT, specifically neuroplasticity in LDT cholinergic neurons induced by cocaine and its functional roles in the development and modulation of addictive behaviors associated with cocaine.

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Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress

Cited by 40 publications

References 84 publications

Kappa opioid receptor binding in major depression: A pilot study

Kappa opioid receptor binding in major depression: A pilot study

Non-pharmacological factors that determine drug use and addiction

Neuroplasticity in cholinergic neurons of the laterodorsal tegmental nucleus contributes to the development of cocaine addiction

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