There is a high degree of overlap between brain regions involved in processing natural rewards and drugs of abuse. “Non-drug” or “behavioral” addictions have become increasingly documented in the ...clinic, and pathologies include compulsive activities such as shopping, eating, exercising, sexual behavior, and gambling. Like drug addiction, non-drug addictions manifest in symptoms including craving, impaired control over the behavior, tolerance, withdrawal, and high rates of relapse. These alterations in behavior suggest that plasticity may be occurring in brain regions associated with drug addiction. In this review, I summarize data demonstrating that exposure to non-drug rewards can alter neural plasticity in regions of the brain that are affected by drugs of abuse. Research suggests that there are several similarities between neuroplasticity induced by natural and drug rewards and that, depending on the reward, repeated exposure to natural rewards might induce neuroplasticity that either promotes or counteracts addictive behavior.
This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’.
► Disorders such as compulsive gambling and eating have been compared to addiction. ► Drug addiction is associated with neuroplasticity in mesocorticolimbic circuitry. ► I compare/contrast plasticity associated with exposure to drug and non-drug rewards. ► Exposure to high fat/sugar foods or sex induces plasticity similar to drugs of abuse. ► Exercise/enrichment induces plasticity opposite to drugs and lowers drug-seeking.
To evaluate trends and correlates of methamphetamine use in the United States.
Data are from 15 747 334 drug-related treatment admissions among persons aged 12 years or older in the 2008-2017 ...Treatment Episode Data Set. We analyzed trends and used multivariable logistic regression.
Methamphetamine-related admissions increased from 15.1% of drug-related treatment admissions in 2008 to 23.6% in 2017. Increases occurred among nearly all demographic groups. Methamphetamine injection increased from 17.5% of admissions in 2008 to 28.4% in 2017. Among methamphetamine-related admissions, heroin use increased from 5.3% of admissions in 2008 to 23.6% in 2017. Characteristics associated with increased odds of reporting methamphetamine use at admission included female sex; admissions aged 35 to 44 years; admissions in the Midwest, South, and West; unemployment; not in labor force; living dependent; living homeless; and having a referral from criminal justice, a health care provider, or other community treatment source.
Treatment admissions involving methamphetamine use increased significantly over the past decade and appear to be linked to the ongoing opioid crisis in the United States. Efforts to mobilize public health prevention, treatment, and response strategies to address rising methamphetamine use and overdose are needed.
The Arctic icescape is rapidly transforming from a thicker multiyear ice cover to a thinner and largely seasonal first-year ice cover with significant consequences for Arctic primary production. One ...critical challenge is to understand how productivity will change within the next decades. Recent studies have reported extensive phytoplankton blooms beneath ponded sea ice during summer, indicating that satellite-based Arctic annual primary production estimates may be significantly underestimated. Here we present a unique time-series of a phytoplankton spring bloom observed beneath snow-covered Arctic pack ice. The bloom, dominated by the haptophyte algae Phaeocystis pouchetii, caused near depletion of the surface nitrate inventory and a decline in dissolved inorganic carbon by 16 ± 6 g C m
. Ocean circulation characteristics in the area indicated that the bloom developed in situ despite the snow-covered sea ice. Leads in the dynamic ice cover provided added sunlight necessary to initiate and sustain the bloom. Phytoplankton blooms beneath snow-covered ice might become more common and widespread in the future Arctic Ocean with frequent lead formation due to thinner and more dynamic sea ice despite projected increases in high-Arctic snowfall. This could alter productivity, marine food webs and carbon sequestration in the Arctic Ocean.
There is a high co-occurrence of risky substance use among adults with traumatic brain injury (TBI), although it is unknown if the neurologic sequelae of TBI can promote this behavior. We propose ...that to conclude that TBI can cause risky substance use, it must be determined that TBI precedes risky substance use, that confounders with the potential to increase the likelihood of both TBI and risky substance use must be ruled out, and that there must be a plausible mechanism of action. In this review, we address these factors by providing an overview of key clinical and preclinical studies and list plausible mechanisms by which TBI could increase risky substance use. Human and animal studies have identified an association between TBI and risky substance use, although the strength of this association varies. Factors that may limit detection of this relationship include differential variability due to substance, sex, age of injury, and confounders that may influence the likelihood of both TBI and risky substance use. We propose possible mechanisms by which TBI could increase substance use that include damage-associated neuroplasticity, chronic changes in neuroimmune signaling, and TBI-associated alterations in brain networks.
DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity, and behavior. Here we used a structure-based approach to develop a new Gi-coupled DREADD using ...the kappa-opioid receptor as a template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq-coupled M3-DREADD within the same neuronal population facilitated the sequential and bidirectional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.
•Structure-guided approach for κ-opioid receptor (KOR)-DREADD (KORD) design•KORD is selectively activated by salvinorin B, and not by endogenous opioids•KORD robustly silenced multiple neuronal subtypes•Inhibitory KORD combined with excitatory hM3Dq for multiplexed behavioral control
The κ-opioid receptor (KOR) was used as a template to generate a novel inhibitory DREADD (KORD), which is activated by salvinorin B and insensitive to endogenous opioid peptides. Sequential activation of the inhibitory KOR-DREADD and an excitatory M3-DREADD facilitated the bidirectional, multiplexed modulation of behavior.
Several preclinical studies have demonstrated that environmental enrichment (EE) during abstinence reduces drug seeking for psychostimulant and opioid drugs. Drug seeking is dependent on activity ...within the dorsomedial prefrontal cortex, and enrichment has been able to reduce drug seeking-associated increases in c-Fos in this region. In this study, we tested the hypothesis that EE during abstinence from oxycodone self-administration would reduce drug seeking and c-Fos immunoreactivity within the prefrontal cortex in a cell-type specific manner.
Male rats self-administered oxycodone in two-hours sessions for three weeks, then underwent an initial drug seeking test under extinction conditions after one week of forced abstinence. Following this test, rats received either EE or remained individually housed in their home cage, then a second drug seeking test, with tissue collection immediately afterward.
Compared to rats in standard housing, environmentally enriched rats had lower oxycodone seeking. In the prelimbic and infralimbic prefrontal cortices, the number of c-Fos+ cells was reduced, and this reduction was predominantly in inhibitory cells neurons, as evidenced by a reduction in the proportion of c-Fos+ cells in GAD+, but not CamKII+ cells. There was also a robust positive relationship between the number of c-Fos+ cells and persistence of oxycodone seeking in both the PrL and IL.
These findings further support the effectiveness of enriched environments to reduce reactivity to drug-associated stimuli and contexts and provide a potential mechanism by which this occurs.
•Environmental enrichment during abstinence sharply reduced oxycodone seeking•Environmental enrichment reduced Fos in prelimbic and infralimbic cortices•Environmental enrichment selectively reduced Fos in GAD67+ neurons.
Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of ...the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells.
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► The recognition specificity of 70 SH2 domains is probed ► Recognition specificity diverges faster than sequence ► PepspotDB is a database of protein interactions mediated by SH2 domains
Cells respond to growth factors and additional external and internal molecular cues by changing their tyrosine phosphorylation profile. This in turn triggers the modulation of complexes that read and process the information. Cesareni and colleagues now help to define the code that permits recognition of phosphotyrosine residues by SH2 domains, the most abundant class of phosphotyrosine binding domains.
Astrocyte heterogeneity is an emerging concept in which astrocytes within or between brain regions show variable morphological and/or gene expression profiles that presumably reflect different ...functional roles. Recent evidence indicates that retrotrapezoid nucleus (RTN) astrocytes sense changes in tissue CO2/H+ to regulate respiratory activity; however, mechanism(s) by which they do so remain unclear. Alterations in inward K+ currents represent a potential mechanism by which CO2/H+ signals may be conveyed to neurons. Here, we use slice electrophysiology in rats of either sex to show that RTN astrocytes intrinsically respond to CO2/H+ by inhibition of an inward rectifying potassium (Kir) conductance and depolarization of the membrane, while cortical astrocytes do not exhibit such CO2/H+‐sensitive properties. Application of Ba2+ mimics the effect of CO2/H+ on RTN astrocytes as measured by reductions in astrocyte Kir‐like currents and increased RTN neuronal firing. These CO2/H+‐sensitive currents increase developmentally, in parallel to an increased expression in Kir4.1 and Kir5.1 in the brainstem. Finally, the involvement of Kir5.1 in the CO2/H+‐sensitive current was verified using a Kir5.1 KO rat. These data suggest that Kir inhibition by CO2/H+ may govern the degree to which astrocytes mediate downstream chemoreceptive signaling events through cell‐autonomous mechanisms. These results identify Kir channels as potentially important regional CO2/H+ sensors early in development, thus expanding our understanding of how astrocyte heterogeneity may uniquely support specific neural circuits and behaviors.
Main Points
Astrocytes in the RTN but not cortex intrinsically sense CO2/H+ by inhibition of a Kir conductance.
Inhibition of astrocyte Kir is sufficient to increase RTN neuronal firing.
Chemosensitivity of RTN astrocytes is dependent on Kir4.1/5.1 channels.
Hypothalamic-pituitary-adrenal (HPA) axis dynamics are disrupted by opioids and may be involved in substance abuse; this persists during withdrawal and abstinence and is associated with co-morbid ...sleep disruption leading to vulnerability to relapse. We hypothesized that chronic sleep restriction (SR) alters the HPA axis diurnal rhythm and the sexually dimorphic response to acute stressor during opioid abstinence. We developed a rat model to evaluate the effect of persistent sleep loss during opioid abstinence on HPA axis dynamics in male and female rats. Plasma ACTH and corticosterone were measured diurnally and in response to acute restraint stress in rats Before (control) compared to During subsequent opioid abstinence without or with SR. Abstinence, regardless of sleep state, led to an increase in plasma ACTH and corticosterone in the morning in males. There was a tendency for higher PM plasma ACTH during abstinence in SR males (p = 0.076). ACTH and corticosterone responses to restraint were reduced in male SR rats whereas there was a failure to achieve the post-restraint nadir in female SR rats. There was no effect of the treatments or interventions on adrenal weight normalized to body weight. SR resulted in a dramatic increase in hypothalamic PVN AVP mRNA and plasma copeptin in male but not female rats. This corresponded to the attenuation of the HPA axis stress response in SR males during opioid abstinence. We have identified a potentially unique, sexually dimorphic role for magnocellular vasopressin in the control of the HPA axis during opioid abstinence and sleep restriction.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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