Ox2

The present study, regarding the orexin receptors having a pivotal role in reward-related psychostimulant use disorder (PUD), aimed to investigate the role of orexin-2 (OX2) receptors in the CA1 region of the hippocampus (HPC) in the extinction and reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP). In the first set of investigations, to determine the role of OX2 receptors in the extinction of METH-induced CPP, rats were daily given (during the extinction) bilaterally intra-CA1 region different doses of TCS OX2 29 (1, 3, 10, and 30 nmol/0...

PURPOSE: The interaction of orexinergic neurons with the opioidergic system and their effects on morphine analgesia and tolerance have not been fully elucidated. The purpose of the study was to evaluate the effects of the orexin-1 and orexin-2 receptor (OX1R and OX2R) agonist and antagonist on morphine analgesia and tolerance in rats. MATERIAL AND METHODS: A total of 90 Wistar albino male rats weighing 180-220 g were used in the experiments. To induce morphine tolerance, rats were injected with a single dose of morphine (50 mg kg-1, s...

Because of the relapsing properties of psychostimulants such as methamphetamine (Meth), there is no established pharmacotherapy for Meth addiction. The orexinergic system is a promising target for treating psychostimulant use disorders and relapse. However, to the best of our knowledge, no investigation regarding the role of orexin receptors in the dentate gyrus (DG) region of the hippocampus has been conducted in the extinction and reinstatement of Meth-seeking behavior. Two stainless-steel guide cannulae were bilaterally implanted into the DG of the rats' brains...

The orexin (hypocretin) system comprises two neuropeptides (orexin-A and orexin-B) and two G-protein coupled receptors (the orexin type 1 and the orexin type 2 receptor). The system regulates several biological functions including appetite, the sleep-wake cycle, the stress response, and motivation and reward processing. Dysfunction of the orexin system has been implicated in the pathophysiology of depression in human and animal studies, although the exact nature of this dysfunction remains unclear. Orexin receptor antagonists (ORAs) are a class of compounds developed for the treatment of insomnia and have demonstrated efficacy in this area...

False shamrock (Oxalis triangularis), native to South America, is an ornamental and popular plant bulb, commercialized for their attractive shape and color (purple triangular leaves) (Taha et al., 2013). In Chile, a rust was detected in O. triangularis plants growing from April to June in several gardens (n=10) in the city of Valdivia, estimating a disease incidence between 80 and 100%. The symptoms appeared as diffuse chlorotic spots from the upperside of leaves, where infected tissues eventually become completely necrotic, and yellow rust pustules were observed on the underside of leaves...

An oxalate-doped hydroxyapatite (O-HAP) was hydrothermally synthesized for aqueous lead (Pb) removal based on the solubility-limiting ability of oxalate and phosphate over pH range 4-9. Free Pb2+ activities in oxalate and/or phosphate systems were controlled by oxalate to form soluble ion pairs Pb-Ox (aq) and Pb-Ox2 2- at pH 4-7 while in preference to persist as PbHPO4 (aq) when pH ≥ 8. Both phosphate and oxalate exhibited excellent efficiency in reducing Pb solubility, causing over 99 % of Pb precipitated from solution following oxalate < oxalate-phosphate < phosphate...

Plant acyl-CoA dominated acyltransferases (named BAHD) comprise a large appointed protein superfamily and play varied roles in plant secondary metabolism like synthesis of modified anthocyanins, flavonoids, volatile esters, etc. Tea ( Camellia sinensis ) is an important non-alcoholic medicinal and fragrancy plant synthesizing different secondary metabolites, including flavonoids. In the tea ( C.A sinensis ) cultivar Longjing 43 (LJ43), eight samples were performed into three groups for transcriptome analysis under three biological replications...

The effects of a nanocarbon solution on the nutrients, glucosinolate metabolism and glucoraphanin pathway in broccoli were investigated. Significant positive linear relationships were observed between the nanocarbon solution and total protein yield, although effects on the soluble sugars, vitamin C and dry matter production were not observed. All nanocarbon solutions significantly increased the glucoraphanin content ( p  < 0.05), and the 18.75 L·ha-1 nanocarbon solution maximally increased the glucoraphanin content by 22...

In this study, the interaction energy ( E int ) of suvorexant (as an orexin receptor antagonist) and some of its analogues with the important residues of the human OX2 orexin receptor, determined by molecular docking, is calculated using the symmetry-adapted perturbation theory-density functional theory (SAPT (DFT)) method. Also, the important residues with the dominant interaction with each ligand are determined based on the obtained SAPT (DFT) interaction energies. To analyze the interaction of the receptor with each ligand, the decomposition of E int to its constituent components including electrostatic ( E ele ), exchange ( E ex ), induction ( E ind ), and exchange-induction ( E ex-ind ), dispersion ( E disp ), and exchange-dispersion ( E ex-disp ) is performed...

As a part of descending pain inhibitory system, orexin (OXs) in the ventral tegmental area (VTA) are implicated in nociceptive responses. The current study aimed to evaluate the role of OX receptors (OXRs) in the VTA in stress-induced analgesia in persistent inflammatory pain. Ninety-nine adult male Wistar rats underwent forced swim stress (FSS) following intra-VTA infusion of various doses of SB334867 or TCS OX2 29 (1, 3, 10, and 30 nmol/0.3 μL) as an OX1R or OX2R antagonist, respectively. The nociceptive threshold was evaluated using the formalin test as an animal model of persistent inflammatory pain...

Exposure to stressful stimuli induces various physiological and behavioral responses, affects pain perception, and alters gene expression. Stress elicits an analgesic effect in laboratory animals, termed the "stress-induced analgesia" (SIA). Orexin neuropeptides, processed from pre-pro-orexin in the hypothalamus, release during stress and are known to be antinociceptive. The current study examined the modulatory role of the ventral tegmental area (VTA) orexinergic system in the restraint SIA and extracellular signal-regulated kinase (ERK) activation in the nucleus accumbens (NAc)...

Purpose of Review: Insomnia is a complex sleeping disorder that affects the lives of many individuals worldwide. Insomnia often occurs in the presence of coexisting comorbidities making it a complex disorder that requires a multifactorial approach to therapy. First-line therapy is cognitive-behavioral therapy for insomnia (CBT-I). Pharmacotherapy for insomnia falls into four classes based on mechanism of action: benzodiazepine receptor agonists (BZRAs), histamine receptor antagonists, melatonin receptor agonists, and dual orexin receptor antagonists (DORAs)...

One of the main obstacles in treating psychostimulant addiction is relapse even after long-term abstinence. The nucleus accumbens (NAc) is located in the basal forebrain, responsible for regulating several behaviors, specifically reward-related effect of psychostimulants. In the current study, an unbiased place conditioning paradigm was performed to inquire the role of the hypocretin/orexin system in the NAc in the extinction and reinstatement of methamphetamine (Meth)-induced conditioned place preference (CPP)...

Overwhelming evidence has revealed that the orexins (OXs) and their receptors in the mesolimbic system participate in modulating psychostimulants and rewarding impacts. The current study aimed to elucidate the role of OX receptors in the ventral tegmental area (VTA) in the acquisition and expression phases of methamphetamine (METH)-induced conditioned place preference (CPP). In the first set of experiments, animals bilaterally received OX receptor 1 (SB 334867) or OX receptor 2 (TCS OX2 29) antagonist (1, 3, 10, and 30 nmol/0...

Background: CA1, as a major structure involved in learning and memory, has been shown to be affected by tramadol addiction. Both orexin and endocannabinoid receptors express in CA1 and play an important role in drug dependency. The aim of this study was to evaluate the modulatory effects of orexin-2 (OX2R) and endocannabinoid-1 (CB1R) receptors on neuronal activity in CA1, in response to tramadol in rats. Materials and Methods: Male Wistar rats were divided into 8 groups ( n = 6-7); saline-dimethyl sulfoxide (DMSO), tramadol-DMSO, saline-TCS-OX2-29, saline-AM251, tramadol-TCS-OX2-29, tramadol-AM251, saline-TCS-OX2-29-AM251, tramadol-TCS-OX2-29-AM251...

Introduction: The Basolateral Amygdala (BLA) substantially affects neuronal transmission and synaptic plasticity processes through the dentate gyrus. Orexin neuropeptides play different roles in the sleep/wakefulness cycle, feeding, learning, and memory. The present study aimed to investigate the function of the orexin receptors of the BLA in the hippocampal local interneuron circuits. Methods: For this, the region's paired-pulse responses from the Dentate Gyrus (DG) were recorded...

The zwitterionic complex formed by NiII and 2,2':6',2″-terpyridine-4'-carboxylate, Ni(tpyc)2 , has been used as a coligand with a diverse group of polycarboxylates in uranyl ion complexes synthesized under solvo-hydrothermal conditions, thus giving a series of 14 mixed ligand, heterometallic compounds. Both [(UO2 )2 ( c -1,2-chdc)Ni(tpyc)2 (NO3 )2 ]2 ·4CH3 CN ( 1 ) and [(UO2 )2 (tdc)Ni(tpyc)2 (NO3 )2 ]2 ( 2 ), where c -1,2-chdc2- is cis -1,2-cyclohexanedicarboxylate and tdc2- is 2,5-thiophenedicarboxylate, display discrete U4 Ni2 dinickelatetrauranacycles, a motif which is also found as part of a daisychain coordination polymer in [(UO2 )4 (bdc)3 Ni2 (tpyc)4 (NO3 )2 ]·2CH3 CN·2H2 O ( 3 ), where bdc2- is 1,4-benzenedicarboxylate...

The OX2 orexin receptor (OX2 R) is a highly expressed G protein-coupled receptor (GPCR) in the brain that regulates wakefulness and circadian rhythms in humans. Antagonism of OX2 R is a proven therapeutic strategy for insomnia drugs, and agonism of OX2 R is a potentially powerful approach for narcolepsy type 1, which is characterized by the death of orexinergic neurons. Until recently, agonism of OX2 R had been considered 'undruggable.' We harness cryo-electron microscopy of OX2 R-G protein complexes to determine how the first clinically tested OX2 R agonist TAK-925 can activate OX2 R in a highly selective manner...

Hypoglycaemia is a common side-effect of the treatment of type 1 diabetes with insulin. The Diabetes Control and Complications Trial indicated that, while intensive insulin therapy reduced the incidence and severity of diabetic complications such as retinopathy, neuropathy and nephropathy, the incidence of severe hypoglycaemia was increased 2-3 fold. In non-diabetic individuals, hypoglycaemia triggers the glucose counter-regulatory response. This response consists of inhibition of insulin secretion and activation of glucagon secretion...

The identification and study of supramolecular synthons is a fundamental task in the design of pharmaceutical cocrystals. The malaria drug pyrimethamine (pyr) and the antibiotic trimethoprim (tmp) are both 2,4-diaminopyrimidine derivatives, providing the same C-NH2 /N=C/C-NH2 and C-NH2 /N=C interaction sites. In this article, we analyze and compare the synthons observed in the crystal structures of tmp and pyr cocrystals and molecular salts with sulfamethazine (smz), α-ketoglutaric acid (keto), oxalic acid (ox), sebacic acid (seb), and azeliac acid (az)...