Endogenous and Exogenous Opioids in Pain

Annual Review of Neuroscience, Год журнала: 2018, Номер 41(1), С. 453 - 473

Опубликована: Май 31, 2018

Opioids are the most commonly used and effective analgesic treatments for severe pain, but they have recently come under scrutiny owing to epidemic levels of abuse overdose. These compounds act on endogenous opioid system, which comprises four G protein-coupled receptors (mu, delta, kappa, nociceptin) major peptide families (β-endorphin, enkephalins, dynorphins, nociceptin/orphanin FQ). In this review, we first describe functional organization pharmacology system. We then summarize current knowledge signaling mechanisms by opioids regulate neuronal function neurotransmission. Finally, discuss loci action along peripheral central pain pathways, emphasizing pain-relieving properties against affective dimension experience.

Язык: Английский

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Opioid receptors: drivers to addiction?

Nature reviews. Neuroscience, Год журнала: 2018, Номер 19(8), С. 499 - 514

Опубликована: Июнь 22, 2018

Язык: Английский

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Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior

eLife, Год журнала: 2017, Номер 6

Опубликована: Июль 14, 2017

Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural behavior, downstream receptors anatomical projections mediate these acute risk behavioral states via LC-NE system remain unresolved. Here we use a combination retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, in vivo optogenetics with localized pharmacology to identify substrates increased mice. We demonstrate photostimulation fibers BLA evokes norepinephrine release basolateral amygdala (BLA), alters neuronal activity, conditions aversion, increases Additionally, report β-adrenergic phenotype NE BLA. These studies begin illustrate how complex efferent selectively mediates behavior through distinct receptor projection-selective mechanisms.

Язык: Английский

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A Motivational and Neuropeptidergic Hub: Anatomical and Functional Diversity within the Nucleus Accumbens Shell

Neuron, Год журнала: 2019, Номер 102(3), С. 529 - 552

Опубликована: Май 1, 2019

Язык: Английский

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The central extended amygdala in fear and anxiety: Closing the gap between mechanistic and neuroimaging research

Neuroscience Letters, Год журнала: 2017, Номер 693, С. 58 - 67

Опубликована: Ноя. 30, 2017

Язык: Английский

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Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System

Neuron, Год журнала: 2019, Номер 102(3), С. 564 - 573.e6

Опубликована: Март 13, 2019

Язык: Английский

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Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Июнь 15, 2022

Opioids mediate their effects via opioid receptors: mu, delta, and kappa. At the neuronal level, receptors are generally inhibitory, presynaptically reducing neurotransmitter release postsynaptically hyperpolarizing neurons. However, receptor-mediated regulation of function synaptic transmission is not uniform in expression pattern mechanism across brain. The localization within specific cell types neurocircuits determine that endogenous exogenous opioids have on brain function. In this review we will explore similarities differences neurotransmission different regions. We discuss how future studies can consider potential cell-type, regional, neural pathway-specific order to better understand modulate

Язык: Английский

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Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity

Neuron, Год журнала: 2017, Номер 93(1), С. 147 - 163

Опубликована: Янв. 1, 2017

Язык: Английский

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A Central Extended Amygdala Circuit That Modulates Anxiety

Journal of Neuroscience, Год журнала: 2018, Номер 38(24), С. 5567 - 5583

Опубликована: Май 21, 2018

Both the amygdala and bed nucleus of stria terminalis (BNST) have been implicated in maladaptive anxiety characteristics disorders. However, underlying circuit cellular mechanisms remained elusive. Here we show that mice with Erbb4 gene deficiency somatostatin-expressing (SOM+) neurons exhibit heightened as measured elevated plus maze test open field test, two assays commonly used to assess anxiety-related behaviors rodents. Using a combination electrophysiological, molecular, genetic, pharmacological techniques, demonstrate abnormal mutant is caused by enhanced excitatory synaptic inputs onto SOM+ central (CeA), resulting reduction inhibition downstream BNST. Notably, our results indicate an increase dynorphin signaling CeA mediates paradoxical BNST neurons, consequent activity both necessary for sufficient drive anxiety. Finally, associated dysfunctions increased CeA-BNST can be recapitulated stress wild-type mice. Together, unravel previously unknown processes extended cause anxiety.SIGNIFICANCE STATEMENT The has behaviors, but are unclear. found (CeA) controls through modulation terminalis, process mediated CeA. Our reveal may account

Язык: Английский

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Role of the bed nucleus of the stria terminalis in aversive learning and memory

Learning & Memory, Год журнала: 2017, Номер 24(9), С. 480 - 491

Опубликована: Авг. 16, 2017

Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, freezing behavior). The bed nucleus of stria terminalis (BNST) is a critical interface between "affective forebrain"-including amygdala, ventral hippocampus, medial prefrontal cortex-and hypothalamic brainstem areas that have been implicated neuroendocrine, autonomic, behavioral to actual or anticipated threats. However, precise contribution BNST behavior unclear, both terms antecedent stimuli mobilize activity consequent reactions. For example, it well known essential contextual fear conditioning, but dispensable conditioning discrete conditioned (CSs), at least as indexed by behavior. recent evidence suggests there are circumstances which may persist independent BNST. Furthermore, involved reinstatement relapse) extinguished CSs. As such, gaps understanding how contributes fundamental processes Pavlovian conditioning. Here, we attempt provide an integrative account function We discuss distinctions unconditioned role organizing behaviors associated with these states. propose mediates responses-not based on modality duration threat response threat-but rather consequence ability stimulus predict when aversive outcome will occur (i.e., its temporal predictability). argue not uniquely mobilized sustained responses. In contrast, poorly

Язык: Английский

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