Effects of oxytocin receptor agonism on acquisition and expression of pair bonding in male prairie voles.

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats.

Effects of social housing on alcohol intake in mice depend on the non-social environment.

Background: Excessive alcohol consumption leads to serious health problems. Mechanisms regulating the consumption of alcohol are insufficiently understood. Previous preclinical studies suggested that non-social environmental and social environmental complexities can regulate alcohol consumption in opposite directions.

Effects of Oxytocin Receptor Agonism on Acquisition and Expression of Pair Bonding in Male Prairie Voles.

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats.

CFA-treated mice induce hyperalgesia in healthy mice via an olfactory mechanism.

Background: Social interactions with subjects experiencing pain can increase nociceptive sensitivity in observers, even without direct physical contact. In previous experiments, extended indirect exposure to soiled bedding from mice with alcohol withdrawal-related hyperalgesia enhanced nociception in their conspecifics. This finding suggested that olfactory cues could be sufficient for nociceptive hypersensitivity in otherwise untreated animals (also known as "bystanders").

Characterization of social hierarchy formation and maintenance in same-sex, group-housed male and female C57BL/6 J mice.

Social hierarchies are a prevalent feature of all animal groups, and an individual's rank within the group can significantly affect their overall health, typically at the greatest expense of the lowest-ranked individuals, or omegas. These subjects have been shown to exhibit various stress-related phenotypes, such as increased hypothalamic-pituitary axis activity and increased amygdalar corticotropin-releasing factor levels compared to higher-ranked subjects. However, these findings have been primarily characterized in males and in models requiring exhibition of severe aggression.

Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE.

Targeting the oxytocin (OXT) peptide system has emerged as a promising new approach for the treatment of alcohol use disorder (AUD). However, further advancements in this development depend on properly modeling various complex social aspects of AUD and its treatment. Here we examined behavioral and molecular underpinnings of OXT receptor (OXTR) agonism in prairie voles, a rodent species with demonstrated translational validity for neurobiological mechanisms regulating social affiliations.

Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder.

Development of better treatments for alcohol use disorder (AUD) is urgently needed. One promising opportunity for this development is the potential of targeting the oxytocin peptide system. Preclinical studies showed that administration of exogenous oxytocin or, more recently, stimulation of neurons expressing endogenous oxytocin lead to a decreased alcohol consumption across several rodent models.

Hyperbaric oxygen produces a nitric oxide synthase-regulated anti-allodynic effect in rats with paclitaxel-induced neuropathic pain.

Research has demonstrated that hyperbaric oxygen (HBO) treatment produced relief of both acute and chronic pain in patients and animal models. However, the mechanism of HBO antinociceptive effect is still elusive. Based on our earlier findings that implicate NO in the acute antinociceptive effect of HBO, the purpose of this study was to ascertain whether HBO-induced antinociception in a chronic neuropathic pain model is likewise dependent on NO.

nNOS immunoreactivity co-localizes with GABAergic and cholinergic neurons, and associates with β-endorphinergic and met-enkephalinergic opioidergic fibers in rostral ventromedial medulla and A5 of the mouse.

The present study examined the co-expression of neuronal nitric oxide synthase (nNOS) in the rostral ventromedial medulla (RVM) and A5 regions of the mouse brainstem within several neurochemical populations involved in nociceptive modulation. Double immunohistochemical methods showed that nNOS+ neurons do not co-localize with serotonergic neurons within any of these regions. Within the RVM, the nuclei raphe magnus and gigantocellularis contain a population of nNOS+/GAD67+ neurons, and within the paragigantocellularis lateralis, there is a smaller population of nNOS+/CHAT+ neurons.

Optogenetic Evidence for a Direct Circuit Linking Nociceptive Transmission through the Parabrachial Complex with Pain-Modulating Neurons of the Rostral Ventromedial Medulla (RVM).

The parabrachial complex (PB) is a functionally and anatomically complex structure involved in a range of homeostatic and sensory functions, including nociceptive transmission. There is also evidence that PB can engage descending pain-modulating systems, the best characterized of which is the rostral ventromedial medulla (RVM). Two distinct classes of RVM neurons, "ON-cells" and "OFF-cells," exert net pronociceptive and anti-nociceptive effects, respectively.

Hyperbaric oxygen treatment suppresses withdrawal signs in morphine-dependent mice.

Hyperbaric oxygen (HBO2) therapy reportedly reduces opiate withdrawal in human subjects. The purpose of this research was to determine whether HBO2 treatment could suppress physical signs of withdrawal in opiate-dependent mice. Male NIH Swiss mice were injected s.

Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice.

Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2) can elicit an antinociceptive response in models of acute pain. We have demonstrated that this antinociceptive effect is centrally-mediated and is dependent on opioid receptors. The purpose of the present study was to examine the role of endogenous opioid peptides and opioid receptors specifically in the spinal cord in the acute antinociceptive effect of HBO2 in mice.

Involvement of brain opioid receptors in the anti-allodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain.

Earlier research has demonstrated that hyperbaric oxygen (HBO2) can produce an antinociceptive effect in models of acute pain. Recent studies have revealed that HBO2 can produce pain relief in animal models of chronic pain as well. The purpose of the present investigation was to ascertain whether HBO2 treatment might suppress allodynia in rats with neuropathic pain and whether this effect might be blocked by the opioid antagonist naltrexone (NTX).

Novel monofunctional platinum (II) complex Mono-Pt induces apoptosis-independent autophagic cell death in human ovarian carcinoma cells, distinct from cisplatin.

Failure to engage apoptosis appears to be a leading mechanism of resistance to traditional platinum drugs in patients with ovarian cancer. Therefore, an alternative strategy to induce cell death is needed for the chemotherapy of this apoptosis-resistant cancer. Here we report that autophagic cell death, distinct from cisplatin-induced apoptosis, is triggered by a novel monofunctional platinum (II) complex named Mono-Pt in human ovarian carcinoma cells.

Stereospecific analytical method development and preliminary in vivo pharmacokinetic characterization of pinostrobin in the rat.

The complete pharmacokinetic disposition of the chiral flavonoid (±) pinostrobin remains unknown without the development of an analytical method of detection and quantitation of its individual enantiomers. Resolution of the enantiomers of pinostrobin was achieved using as simple high-performance liquid chromatographic method. A Chiralpak(®) AD-RH column was employed to perform baseline separation with UV detection at 287 nm.

Cytotoxic palladium(II) complexes of 8-aminoquinoline derivatives and the interaction with human serum albumin.

Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdL(n)Cl] [L(1) = N-(tert-butoxycarbonyl)-l-methionine-N'-8-quinolylamide, L(2) = L-alanine-N'-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography.

Cellular and biomolecular responses of human ovarian cancer cells to cytostatic dinuclear platinum(II) complexes.

Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH₃)₂Cl]₂L¹}(NO₃)₂ (1) and {[cis-Pt(NH₃)₂Cl]₂L²}(NO₃)₂ (2) (L¹ = α,α'-diamino-p-xylene, L² = 4,4'-methylenedianiline) has been studied using cisplatin as a reference.

Reversible DNA condensation induced by a tetranuclear nickel(II) complex.

DNA condensing agents play a critical role in gene therapy. A tetranuclear nickel(II) complex, [Ni(II)(4)(L-2H)(H(2)O)(6)(CH(3)CH(2)OH)(2)]·6NO(3) (L=3,3',5,5'-tetrakis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4'-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P2(1)/n, a=10.

DNA-binding affinity and nuclease activity of two cytotoxic copper terpyridine complexes.

Two copper(II) terpyridine complexes, [Cu(atpy)(NO(3))(H(2)O)](NO(3)) 3H(2)O (1) and [Cu(ttpy)(NO(3))(2)] (2) (atpy = 4'-p-N9-adeninylmethyl-phenyl-2,2':6,2''-terpyridine; ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) exhibited high cytotoxicity, with average ten times more potency than cisplatin against the human cervix carcinoma cell line (HeLa), the human liver carcinoma cell line (HepG2), the human galactophore carcinoma cell line (MCF7), and the human prostate carcinoma cell line (PC-3). The cytotoxicity of the complex 1 was lower than that of the complex 2. Both complexes showed more efficient oxidative DNA cleavage activity under irradiation with UV light at 260 nm than in the presence of ascorbic acid.

Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin.

Clinical application of platinum-based anticancer drugs is largely limited by severe general toxicity and drug resistance. Drug delivery systems with tumor-targeting potential are highly desired for improving the efficacy and applicability of these drugs. This study describes an alternative strategy for the delivery of platinum drugs (cisplatin, carboplatin and oxaliplatin) by encapsulating each of them in the cavity of apoferritin (AFt).

Molecular combo of photodynamic therapeutic agent silicon(iv) phthalocyanine and anticancer drug cisplatin.

The combination of a red light PDT agent and a Pt(ii)-based chemotherapeutic drug at the molecular level maintains the intrinsic functions of each unit; the conjugated complexes exhibit remarkable photocytoxicity and demonstrate potential to serve as agents for DNA-targeting PDT as well as red light photochemotherapy.

DNA binding property, nuclease activity and cytotoxicity of Zn(II) complexes of terpyridine derivatives.

Two zinc(II) terpyridine complexes Zn(atpy)(2)(PF(6))(2) (1) (atpy = 4'-p-N9'-adeninylmethylphenyl-2,2':6,2''-terpyridine) and Zn(ttpy)(2)(PF(6))(2) (2) (ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) have been synthesized and characterized by elemental analysis, (1)H NMR and electrospray mass spectroscopy. The structure of complex 2 was also determined by X-ray crystallography, which revealed a ZnN(6) coordination in an octahedral geometry with two terpyridine acting as equatorial ligands. The circular dichroism data showed that complex 1 exhibited an ICD signal at around 300 nm and induced more evident disturbances on DNA base stacking than complex 2, reflecting the impact of the adenine moiety on DNA binding modes.

Effect of adenine moiety on DNA binding property of copper(II)-terpyridine complexes.

Two novel copper(ii) terpyridine complexes, [Cu(atpy)(NO(3))(H(2)O)](NO(3)).3H(2)O () and [Cu(ttpy)(NO(3))(2)] () (atpy = 4'-p-N9-adeninylmethylphenyl-2,2':6,2''-terpyridine; ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) have been prepared and structurally characterized by X-ray crystallography. Both complexes show a CuN(3)O(2) coordination in a square pyramidal (4 + 1) geometry with terpyridine acting as an equatorial ligand.

DNA binding properties of novel cytotoxic gold(III) complexes of terpyridine ligands: the impact of steric and electrostatic effects.

Four gold(III) complexes of terpyridine derivatives 1-4 have been synthesized and characterized by spectroscopic methods. In vitro data demonstrated that all of them showed higher cytotoxicity than cisplatin against the human non-small-cell lung cancer cell line (A-549), the human stomach carcinoma cell line (SGC-7901), the human cervix carcinoma cell line (HELA), the human colon carcinoma cell line (HCT-116), the human liver carcinoma cell line (BEL-7402), the murine leukemia cell line (P-388) and the human acute promyelocytic leukemia cell line (HL-60). Complex 3 exhibits the highest activity, with growth inhibition rates of over 80% at 10(-8) mol L(-1) against the A-549, HCT-116 and HELA tumor cell lines.