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Nature Communications Oct 2022The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms...
The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAc) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAc neurons impairs reward seeking behavior, while silencing of NAc or NAc→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
Topics: Mice; Animals; Nucleus Accumbens; Reward; Ventral Tegmental Area; Dopaminergic Neurons; Opiate Alkaloids
PubMed: 36271048
DOI: 10.1038/s41467-022-33843-3 -
Canadian Family Physician Medecin de... Dec 2020
Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Humans; Naloxone; Opioid-Related Disorders; Substance Withdrawal Syndrome
PubMed: 33334955
DOI: 10.46747/cfp.6612891 -
American Journal of Respiratory and... Aug 2020
Topics: Critical Care; Humans; Intensive Care Units; Opiate Alkaloids; Patient Discharge; Respiration, Artificial
PubMed: 32464072
DOI: 10.1164/rccm.202005-1815ED -
Cancer Epidemiology, Biomarkers &... Mar 2020There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.
BACKGROUND
There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.
METHODS
Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose.
RESULTS
Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake.
CONCLUSIONS
Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens.
IMPACT
This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.
Topics: Administration, Oral; Adult; Biomarkers; Carcinogens; Cigarette Smoking; Cohort Studies; Humans; Iran; Male; Middle Aged; Opiate Alkaloids; Smoking, Non-Tobacco Products; Tobacco Products
PubMed: 31915141
DOI: 10.1158/1055-9965.EPI-19-1212 -
British Journal of Hospital Medicine... Sep 2022The forearm is the most common site of fracture in children. At the time of initial assessment, a thorough examination and neurovascular assessment of the limb is... (Review)
Review
The forearm is the most common site of fracture in children. At the time of initial assessment, a thorough examination and neurovascular assessment of the limb is necessary. X-rays allow evaluation of the fracture location and type, in addition to the degree of displacement. With the help of intranasal opiates, manipulation of fracture fragments can be performed in the emergency department. Immobilisation in plaster is the gold standard treatment for paediatric forearm fractures where the degree of displacement is within acceptable parameters. Manipulation and casting should be followed by orthogonal radiographs and a repeated neurovascular assessment of the limb. Oral analgesia and safety netting information should be provided on discharge and the child should be reviewed in fracture clinic within a week of the injury. This article reviews the British Orthopaedic Association Standards for Trauma and Orthopaedics for the early management of paediatric forearm fractures that do not require operative management.
Topics: Child; Forearm; Forearm Injuries; Humans; Opiate Alkaloids; Radiography; Radius Fractures
PubMed: 36193916
DOI: 10.12968/hmed.2021.0564 -
ACS Chemical Neuroscience Sep 2017Opioids are among the most effective pain relievers; however, their abuse has been on the rise worldwide evident from an alarming increase in accidental opioid... (Review)
Review
Opioids are among the most effective pain relievers; however, their abuse has been on the rise worldwide evident from an alarming increase in accidental opioid overdoses. This demands for an urgent increase in scientific endeavors for better understanding of main cellular mechanisms and circuits involved in opiate addiction. Preclinical studies strongly suggest that memories associated with positive and negative opioid experiences are critical in promoting compulsive opiate-seeking and opiate-taking behaviors, and relapse. Particular focus on synaptic plasticity as the cellular correlate of learning and memory has rapidly evolved in drug addiction field over the past two decades. Several critical addiction-related brain areas are identified, one of which is the ventral tegmental area (VTA), an area intensively studied as the initial locus for drug reward. Here, we provide an update to our previous review on "Opiates and Plasticity" highlighting the most recent discoveries of synaptic plasticity associated with opiates in the VTA. Electrophysiological studies of plasticity of addiction to date have been invaluable in addressing learning processes and mechanisms that underlie motivated and addictive behaviors, and now with the availability of powerful technologies of transgenic approaches and optogenetics, circuit-based studies hold high promise in fostering synaptic studies of opiate addiction.
Topics: Analgesics, Opioid; Animals; Epigenesis, Genetic; Humans; Neuronal Plasticity; Opiate Alkaloids; Opioid-Related Disorders; Synapses; Ventral Tegmental Area
PubMed: 28768409
DOI: 10.1021/acschemneuro.7b00281 -
American Journal of Respiratory and... Sep 2021
Topics: Analgesia; Delirium; Humans; Opiate Alkaloids; Pain; Pain Management
PubMed: 33956575
DOI: 10.1164/rccm.202104-0968ED -
Molecules (Basel, Switzerland) Apr 20226,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a... (Review)
Review
6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged structural motif originates from a [4 + 2] cycloaddition of morphinan-6,8-dienes with dienophiles. Certain 6,14-ethenomorphinans having extremely high affinity for opioid receptors are often non-selective for opioid receptor subtypes, but this view is now undergoing some revision. The agonist 20-etorphine and 20-dihydroetorphine are several thousand times more potent analgesics than morphine, whereas diprenorphine is a high-affinity non-selective antagonist. The partial agonist buprenorphine is used as an analgesic in the management of post-operative pain or in substitution therapy for opiate addiction, sometimes in combination with the non-selective antagonist naloxone. In the context of the current opioid crisis, we communicated a summary of several decades of work toward generating opioid analgesics with lesser side effects or abuse potential. Our summary placed a focus on Diels-Alder reactions of morphinan-6,8-dienes and subsequent transformations of the cycloadducts. We also summarized the pharmacological aspects of radiolabeled 6,14-ethenomorphinans used in molecular imaging of opioid receptors.
Topics: Analgesics; Analgesics, Opioid; Morphinans; Morphine; Naloxone; Receptors, Opioid; Receptors, Opioid, mu
PubMed: 35566212
DOI: 10.3390/molecules27092863 -
International Journal of Epidemiology Mar 2021Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and...
BACKGROUND
Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.
METHODS
Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.
RESULTS
After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.
CONCLUSIONS
Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.
Topics: Analgesics, Opioid; Cause of Death; Cohort Studies; Diabetes Mellitus; Female; Humans; Iran; Opiate Alkaloids; Prospective Studies; Risk Factors
PubMed: 32810213
DOI: 10.1093/ije/dyaa126 -
Journal of Forensic Sciences Mar 2020
Topics: Amphetamines; Cocaine; Humans; Ketamine; Opiate Alkaloids; Substance-Related Disorders
PubMed: 31995236
DOI: 10.1111/1556-4029.14273