Investigation of Origanum compactum essential oil for analgesic and anti-inflammatory activities

Origanum compactum Benth. has been widely used in moroccan traditional medicine for various therapeutic treatments. Belonging to the same genus, O. onites was found to have marked analgesic and anti-inflammatory activities. The aim of this work is to evaluate theses pharmacological properties of the essential oil of O. compactum in order to provide a basis for the folkloric use of the plant. Aerial parts of plant were subjected to steam distillation, according to the French Pharmacopoeia. Male OF1 mice and male Wistar rats were used for these studies. The analgesic effect was done using Writhing test in mice and Tail-Flick test in rats. The mechanism investigation was evaluated employing an antagonism assay using naloxone, a specific antagonist of opiate receptors. Anti- inflammatory property has been studied using carrageenin and experimental trauma induced edema in rats. The essential oil of the aerial parts of Origanum compactum was found to exert central analgesic properties. Such a dose-dependent action was obtained against chemical and thermic stimuli, respectively, from the doses of 6.25 and 12.5 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. Significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process from the dose of 100 mg/kg.

A Review of Molecular Imaging of Glutamate Receptors

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.

Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents

Slow response to the standard treatment for depression increases suffering and risk of suicide. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, can rapidly alleviate depressive symptoms and reduce suicidality, possibly by decreasing hyperactivity in the lateral habenula (LHb) brain nucleus. Here we find that in a rat model of human depression, opioid antagonists abolish the ability of ketamine to reduce the depression-like behavioral and LHb hyperactive cellular phenotypes. However, activation of opiate receptors alone is not sufficient to produce ketamine-like effects, nor does ketamine mimic the hedonic effects of an opiate, indicating that the opioid system does not mediate the actions of ketamine but rather is permissive. Thus, ketamine does not act as an opiate but its effects require both NMDA and opiate receptor signaling, suggesting that interactions between these two neurotransmitter systems are necessary to achieve an antidepressant effect.

The influence of non-opiate analogue of leu-enkephalin to the cardiac consequences of intrauterine hypoxia of albino rats

Objective ― Our study aimed to evaluate the possibility of correcting cardiac consequences of intrauterine hypoxia (IUH) by injecting leu-enkephalin analog, lacking affinity for opiate receptors, in the early postnatal period. Material and Methods ― To model IUH, we placed pregnant Wistar rats in a hypobaric chamber with an oxygen partial pressure of 52 mmHg. The procedure was repeated for 4 h daily over the 15th-19th days of gestation. From the 2nd through the 6th days of their lives, the offspring were injected intraperitoneally with non-opiate leu-enkephalin analog at a dose of 100 μg/kg (NALE: Phe-D-Ala-Gly-Phe-Leu-Arg). This analog did not have affinity for opiate receptors. The 7- and 60-day old offspring of female rats subjected to IUH were investigated. The control group included the descendants of intact animals. We investigated gravimetric indicators, DNA-synthetic activity of cardiomyocytes (CMC) by tritium-labeled thymidine autoradiography method, the size of the CMC nuclei, as well as size and amount of nucleoli in the CMC nuclei. The activity of free radical oxidation was evaluated in cardiac homogenates by chemiluminescence. Results ― In 7-day old rats subjected to IUH vs. control animals, we observed decreases in body mass by 32.6%, in heart mass by 27.3%; in the proportion of 3Н-thymidine labeled CMC nuclei by 32.7% in the left ventricle and by 30.4% in the right ventricle; in the number of nucleoli in the CMC nuclei (in the left ventricle: control – 2.384±0.027, IUH – 2.282±0.027*, p<0.05; in the right ventricle: control – 2.409±0.038; IUH – 2.240±0.012*, p<0, 05). Increase in CML indices of cardiac homogenates was revealed, indicating the activation of free radical oxidation. In 7-day old rats subjected to IUH and administration of the NALE peptide from the 2nd through the 6th days of their lives, the proportion of 3H-thymidine labeled nuclei in the CMC did not differ from the control (in the left ventricle: control – 12.79±0.89%, IUH + NALE – 10.98±0.95%, p>0.05; in the right ventricle: control – 11.61±0.78%; IUH + NALE – 11.26±0.58%, p>0.05). The number of nucleoli in the CMC nuclei of the left and right ventricles in the heart of 7-day old animals in the IUH + NALE group did not differ from the control too. The CML indices of heart homogenates in the IUH + NALE group were significantly lower than those in the IUH group. In 60-day old male rats exposed to IUH, there was a decrease in heart mass by 18.5%, sizes of CMC nuclei by 7.5% and 16.1% in the left and right ventricles, respectively, and in the total nucleoli area in the CMC nuclei of the left ventricle (control – 3.953±0.085; IUH – 3.372±0.078*; p<0.05). In 60-day old male rats subjected to IUH and injections of the NALE peptide from the 2nd to the 6th days of their lives, heart mass (control – 692.73±26.81 mg; IUH + NALE – 631.0±29.79 mg; p>0.05) and the size of the CMC nuclei of the right ventricle (control – 54.25±0.84; IUH + NALE – 55.24±0.94; p>0.05) did not differ significantly from the control. The size of the nuclei, the number and size of the nucleoli in the CMC of the left ventricle, as well as the area of the nucleoli in the CMC of the right ventricle in 60-day old male rats of the IUH + NALE group significantly exceeded control group values. Conclusion ― Administration of the NALE peptide to albino rats subjected to IUH normalized DNA-synthetic activity and the number of nucleoli in the nuclei of CMC in 7-day old animals, and also reduced the severity of oxidative stress in the heart tissue. In 60-day old albino male rats exposed to IUH, injecting NALE from the 2nd to the 6th days of their lives eliminated declines in heart mass and sizes of the CMC nuclei and nucleoli, and also led to an increase in the values of the nucleus-and-nucleolus complex indices compared with the control.

The effect of various models of cold stress on cytokine production by the cells of the mouse peritoneal cavity under conditions of blockade of opiate receptors

The study of the mechanisms of functioning of the immune system under stress does not lose its relevance for decades. An important factor in the neuroendocrine regulation of immunity during stress is the endogenous opioid system. In the present work, we evaluated the effect of various cold stress variants on the production of cytokines IL-1β and IL-10 by the cells of the mouse peritoneal cavity under conditions of blockade of opiate receptors. It was established that acute and chronic cold stress, regardless of duration, did not affect the production of IL-1β and increased the production of IL-10 by peritoneal macrophages, this effect was canceled by the introduction of naloxone. The effect of chronic cold stress on IL-10 production depended on cell activation. In all variants of stress, an increase in plasma corticosterone concentration was observed, which did not depend on the blockade of opiate receptors. The work was performed in the framework of the state task, the number of the state registration of the topic No. 01201353248.

Genetic differences in opiate receptors

The 1975 manuscript ‘Opioid receptors in mice: Genetic differences’ by Baran and colleagues was the first published paper to forward a hypothesis as to what might underlie mouse strain differences in opioid analgesic response. A strain was identified, CXBK, that exhibited both deficient morphine analgesia and low μ‎-opioid receptor density. Further study of this strain over the next two decades proved very useful, and the phenotype of CXBK mice has now been explained at the molecular level. The Baran et al. paper presaged the modern genetic studies of the μ‎-opioid gene, OPRM1, and was an important early example of the very active modern field of pain genetics.