Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Hydrophobic-action-driven removal of six organophosphorus pesticides from tea infusion by modified carbonized bacterial cellulose.

The abuse of organophosphorus pesticides (OPPs) in tea planting makes it easy to transfer from tea into its infusion, bringing potential health risks to consumers. Thus, it is essential to adopt reliable techniques to remove OPPs from tea infusion. In this study, three treatment methods were used to modify carbonized bacterial cellulose (CBC) to improve its adsorption performance. Among them, CBC treated by hydrazine hydrate (N-CBC) had the best adsorption effect, whose removal rate for dicrotophos is 13 times that of CBC. The in-depth study of adsorption mechanism proved that hydrophobic interaction dominated the adsorption of OPPs onto N-CBC. The pseudo-second-order kinetic model and Langmuir isotherm model were more suitable to describe the process. Additionally, there were no significant changes in tea infusion quality after N-CBC treatment. This work clarifies that N-CBC benefitted from simple preparation method, excellent adsorption performance and unique adsorption mechanism has potential applications in tea infusion.

Ultrasound-assisted Pickering Interfacial Catalysis for Transesterification: Optimization of Biodiesel Yield by Response Surface Methodology.

Recently, Pickering interfacial catalyst (PIC) was widely applied for liquid-liquid reactions, in view of not only intensifying the mass transfer through significant reducing both the drop sizes and the diffusion distance, but also supplying a flexible platform for the immobilization of valuable active sites. However, the restriction of the mobility of catalyst somehow decreases the activity of a catalyst. To obtain a promise reaction efficiency, we firstly report a synergistic method to enhance the biphasic reaction by Pickering emulsion and ultrasound concepts, targeted at efficient production of biodiesel. Response surface methodology based on Box-Behnken design was applied to optimize the reaction conditions, such as composition of catalyst, reaction temperature, ultrasound power, methanol to oil molar ratio and catalyst amount. An over 98% yield of biodiesel could be achieved within 2.5 hours by ultrasound assisted Pickering interfacial catalysis, which is over two times higher than that of ultrasound assisted homogeneous transesterification system. Besides, the ultrasound assisted Pickering emulsion shortened the reaction time by 3.6 fold when compared to mechanical stirring assisted Pickering emulsion system.

Functionalized graphene oxide/sodium alginate beads with ion responsiveness for uranium trapping.

Uranium as a strategic and non-renewable resource has been paid close attention to its efficient recovery and reuse from uranium-containing wastewater. Here, a composite bead was prepared by functionalized graphene oxide and sodium alginate (L-Lys-GO/SA) with ion-stimuli responsiveness for achieving U(VI) adsorption. The L-Lys-GO/SA-60 composite beads can selectively adsorb U(VI) with the maximum adsorption capacity (qmax) of 704.22 mg/g. Interestingly, the composite beads will swell under the stimulation of ions, which is more conducive to rapid solid-liquid separation and U(VI) recovery at low energy consumption. More importantly, the composite beads also exhibit high reusability of U(VI) adsorption with excellent life span of 80.11 % adsorption rate after 9 cycles, meaning that the composite beads and technology may be used in extraction and production for U(VI) from uranium-containing wastewater.

Quickly and efficiently remove multiple pesticides in tea infusions by low-cost carbonized bacterial cellulose.

Soaking tea leaves make tea consumers exposure to pesticide residues more easily. However, there are few studies on the removal of pesticides in tea infusions. Therefore, a low-cost carbonized bacterial cellulose material was prepared by direct calcination method, and used to remove multiple pesticides in tea infusions quickly and efficiently. CBC-350 has the best removal efficiency for 9 pesticides and then screened the best adsorption conditions. The adsorption isotherm experiment was carried out and indicated that the adsorption process was in consist with the Freundlich model. The thermodynamic parameters are also calculated. Moreover, the adsorption mechanism was discussed, which suggests that π-π interaction and hydrophobic action are the driving force during the adsorption process. Exhilaratingly, the CBC-350 also has excellent adsorption capacity compared to other adsorbents and can be reused at least five times.

Gut microbiota modulation and anti-inflammatory properties of Xuanbai Chengqi decoction in septic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanbai Chengqi decoction (XBCQ), a traditional Chinese medicine formulation, was reported to have a protective role in a variety of pulmonary infection diseases. However, its mechanism remains uncertain. In the current study, we investigated the potential mechanism of XBCQ, its therapeutic effects on organ injuries induced by sepsis and gut microbiota modulation. MATERIAL AND METHODS: 80 Male Sprague Dawley rats were performed cecal ligation and puncture (CLP) for sepsis model and 60 of them were treated with different doses of XBCQ (3.78, 7.56, 15.12 g/Kg, 20 rats per group) twice per day. After the most valid dose was determined, another 40 rats were divided randomly into four groups: sham group, sham + XBCQ group, sepsis group, sepsis + XBCQ group. The sepsis + XBCQ group was treated with XBCQ by intragastric administration and then twice per day. Feces of the rats were collected and the gut microbiota constituents were analyzed by 16S rDNA sequencing. Histological changes were observed by H&E staining. Occludin content in the colon was determined by immunohistochemical analysis. The concentrations of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The survival rate of septic rats was increased significantly at the dose of 7.56 g/Kg from 50% to 80% at 72 h. The gut microbiota richness and composition were disturbed in septic rats. XBCQ altered the gut microbiota, involving alpha diversity changes, significantly reducing the relative abundance of Bacteroidaceae and ClostridiumXI and increasing that of Firmicutes and Actinobacteria. Furthermore, the relative abundances of Lactobacillus, Butyricicoccus and Bifidobacterium were increased by XBCQ. Moreover, the gut barrier dysfunction was improved by XBCQ through restoring the impaired tight conjunction protein Occludin. The concentration of diamine oxidase was decreased, while the D-lactate level was elevated. Meanwhile, the level of myeloperoxidase (MPO) in the lung tissue of the XBCQ-treated group was reduced. Lung injury was also alleviated by decreased levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and interleukin 10 (IL-10) in bronchoalveolar lavage fluids (BALFs). The relative abundance of potential microbial biomarkers in four groups significantly correlated with the concentration of inflammatory factors in BALFs. CONCLUSIONS: Our results suggested that XBCQ had a protective role against sepsis by modulating the gut microbiota, restoring the intestinal epithelial barrier and decreasing inflammatory responses.

Traditional Chinese Medicines alleviated myocardial ischemia by regulating Qi and promoting blood circulation.

OBJECTIVE: To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ischemia. METHODS: Fifty male Wistar rats were randomly divided into five groups (n = 10) as follows: (a) sham operation (Sham), (b) myocardial ischemia (Model), (c) treatment that regulates Qi (Qi), (d) treatment that promotes blood circulation (Blood), (e) treatment that both regulates Qi and promotes blood circulation (QB). The rat model was established via activities restriction for 6 h followed by tail clamp stimulation for 5 mins every day for 7 d and occlusion left coronary anterior descending artery. Afterwards rats were treated with medicines that regulate Qi and/or promote blood circulation via gavage for 14 d. Behavioral parameters were evaluated using open field and elevated plus-maze tests. The tongue color and sublingual vein were visually examined. Blood flow perfusion of tongue and auricle were detected using PIM Ⅱ. The mesenteric microcirculation was examined via capillaroscopy, and hemodynamics was assessed using a polygraph system. Serum homocysteine (Hcy), creatine kinase isoenzyme (CKMB) levels and endothelin-1 (ET-1) were measured. Hematoxylin and eosin staining and transmission electron microscopy were employed to detect the myocardial morphology and ultrastructure, respectively. RESULTS: Compared with findings in Sham group, rats in model group had coarse hair, dark mucosa of the lips and claw, low activity, and increased anxiety. Compared with findings in Model group, rats in the three treatment groups exhibited a lighter tongue color without an extended and varicose sublingual vein. There were significant increases of auricle blood flow perfusion in the Qi group and tongue bottom blood flow perfusion in the QB group. Compared with findings in Model rats, rats in Blood group exhibited improved mesenteric microcirculation associated with increased mesenteric blood flow and a larger arteriole diameter. Moreover, compared with findings in Model rats, Qi and QB rats exhibited increased left ventricular ± dp/dtmax, decreased serum CKMB, Hcy, ET-1 levels, and reduced myocardial ultrastructural damage. CONCLUSION: Myocardial ischemia damage was suppressed by Traditional Chinese Medicines that regulate Qi and promote blood circulation.

Melatonin Alleviates Neuronal Damage After Intracerebral Hemorrhage in Hyperglycemic Rats.

BACKGROUND: This study sought to investigate a novel effect of melatonin in reducing brain injury in an in vivo hyperglycemic intracerebral hemorrhage (ICH) model and further explore the mechanisms of protection. METHODS: Hyperglycemia ICH was induced in Sprague-Dawley rats by streptozocin injection followed by autologous blood injection into the striatum. A combined approach including RNA-specific depletion, electron microscopy, magnetic resonance, Western blots, and immunohistological staining was applied to quantify the brain injuries after ICH. RESULTS: Hyperglycemia resulted in enlarged hematoma volume, deteriorated brain edema, and aggravated neuronal mitochondria damage 3 days after ICH. Post-treatment with melatonin 2 hours after ICH dose-dependently improved neurological behavioral performance lasting out to 14 days after ICH. This improved neurological function was associated with enhanced structural and functional integrity of mitochondria. Mechanistic studies revealed that melatonin alleviated mitochondria damage in neurons via activating the PPARδ/PGC-1α pathway. Promisingly, melatonin treatment delayed until 6 hours after ICH still reduced brain edema and improved neurological functions. Melatonin supplementation reduces neuronal damage after hyperglycemic ICH by alleviating mitochondria damage in a PPARδ/PGC-1α-dependent manner. CONCLUSION: Melatonin may represent a therapeutic strategy with a wide therapeutic window to reduce brain damage and improve long-term recovery after ICH.

Pro-angiogenic activity of Tongnao decoction on HUVECs in vitro and zebrafish in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongnao Decoction (TND) is a Chinese decoction approved and used in Jiangsu Province Hospital for the treatment of ischemic stroke. It shows conclusive efficiency in the improvement of neurologic impairment and activities of daily living of the patients. AIM OF THE STUDY: Recently, angiogenesis has been recognized as a potential therapeutic strategy for treating cerebral ischemia. This study was aimed to provide comprehensive evidence for the pro-angiogenic effect of TND and characterize the underlying mechanism. MATERIALS AND METHODS: We firstly established the chemical fingerprinting of TND. Then, the in vitro pro-angiogenic activities of TND were tested on human umbilical vein endothelial cells (HUVECs) through cell viability, wound healing and tube formation assays. The in vivo pro-angiogenic effects were evaluated on transgenic zebrafish embryos [Tg (fli-1: EGFP)] through the formation of intersegmental vessels (ISVs), subintestinal vessels (SIVs) and central arteries (CtAs). Lastly, the potential mechanisms of TND were analyzed by a blocking assay with eight pathways-specific kinase inhibitors. RESULTS: TND promoted the proliferation, migration and tube formation of HUVECs. TND also rescued the impairment of ISVs, SIVs and CtAs caused by VRI in a dose-dependent manner in zebrafish embryos. TND could activate vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) and Raf - mitogen-activated protein kinase1/2 (MEK1/2) - extracellular regulated kinase 1/2 (ERK1/2) signaling pathways. CONCLUSION: Our study firstly demonstrated the pro-angiogenic activities of TND. Our work provided evidences for the clinical usage of TND in restoring neurovascular function through promoting angiogenesis in the ischemic cerebral microvascular.

Paeoniflorin inhibits MRGPRX2-mediated pseudo-allergic reaction via calcium signaling pathway.

Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) has been shown to be a pivotal target for pseudo-allergic diseases. Therefore, MRGPRX2 might be a therapeutic target for allergic contact dermatitis, atopic dermatitis, and red man syndrome. Paeoniflorin (PF) was reported to have an antiinflammatory effect in neuroinflammation, enteritis, and so forth. In this study, we investigated the anti-pseudo-allergic effect of PF and the underlying molecular mechanisms. Our results showed that PF can suppress compound 48/80 (C48/80)-induced PCA and MCs degranulation in vivo, in a dose-dependent manner. Moreover, PF can reduce C48/80-induced calcium influx and suppress MC degranulation and chemokines release in vitro. PF can downregulate the phosphorylation levels of key kinases in PLCγ-regulated calcium influx and subsequent cytokine synthesis pathways. Our study revealed that PF could inhibit C48/80-induced allergic responses both in vivo and in vitro. As such, it may be regarded as a novel inhibitor for preventing MRGPRX2-mediated allergic diseases.

Isoprenoids obtained from Cortex Dictamni and their nitric oxide inhibitory activities.

Nine new isoprenoids, named as dictamtrinor-guaianols A (1), B (2), C (3), D (4), and E (5), dictamnorsesquiterpenol A (6), dictamnorsesquiterpenosides B (7) and C (8), as well as dictamtriterpenol A (9), along with eight known compounds (10-17) were obtained from 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the extensive spectroscopic methods and ECD data analysis. Moreover, LC-MS analysis result suggested compounds 2 and 3 were natural products. Furthermore, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model were used to evaluate nitric oxide production inhibitory activities of them, and compounds 2, 3, 5, 6, 8-11, as well as 15-17 displayed significant activities at 40 µM.

Comprehensive Chemical Profiling in the Ethanol Extract of Pluchea indica Aerial Parts by Liquid Chromatography/Mass Spectrometry Analysis of Its Silica Gel Column Chromatography Fractions.

Pluchea indica Less. is a medicine and food dual-use plant, which belongs to the Pluchea genus, Asteraceae family. Its main constituents are quinic acids, flavonoids, thiophenes, phenolic acids, as well as sesquiterpenes. In order to provide a comprehensive chemical profiling of P. indica, an orthogonal chromatography combining reverse-phase chromatography BEHC18 column with a normal-phase chromatography silica column as the separation system and a ESI-Q-Orbitrap MS as the detector in both positive and negative ion modes were used. According to the retention time (tR) and the exact mass-to-charge ratio (m/z), 67 compounds were unambiguously identified by comparing to the standard references. Moreover, 47 compounds were tentatively speculated on the basis of the rules of MS/MS fragmentation pattern and chromatographic elution order generalized from the above-mentioned reference standards. Among them, 10 of them were potentially novel.

Anti-inflammatory constituents from Cortex Dictamni.

Eight new compounds named as dictamalkosides A (1), B (2), C (3), dictamphenosides A (4), B (5), C (6), D (7) and E (8), as well as 23 known ones were obtained from the 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the spectroscopic evidences. Among the known compounds, 14, 17-23, 25-28, and 31 were isolated from Dictamnus genus for the first time; 16 and 24 were firstly isolated from this plant. And the 13C NMR data of 14 was reported here for the first time. Moreover, compounds 1-8, 12, 18-21, 27 and 31 were found to exhibit potential inhibitory effect on LPS-induced NO production at 40 µM for RAW 264.7 macrophages, which suggested alkaloids and phenolic acids might be anti-inflammation therapeutic substance in Cortex Dictamni.

The anti-anaphylactoid effects of hydroxysafflor yellow A on the suppression of mast cell Ca2+ influx and degranulation.

BACKGROUND: Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cell mediators, especially histamine and lipid mediators. Non-IgE-mediated anaphylaxis can occur because of the direct activation of mast cells. Hydroxysafflor yellow A (HSYA) is the main chemical component of safflower (Carthamus tinctorius) and has been reported to have pharmacological activities. However, the anti-anaphylactoid effect of HSYA has not yet been investigated. PURPOSE: The aims of this study were to evaluate the anti-anaphylactoid activity of HSYA in vivo and to investigate the underlying mechanism in vitro. METHODS: The anti-anaphylactoid activity of HSYA was evaluated in a mouse model of hindpaw extravasation. Calcium imaging was used to assess intracellular Ca2+ mobilization. The levels of cytokines and chemokines released by stimulated mast cells were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. RESULTS: HSYA markedly inhibited mast cell degranulation by suppressing the activation of intracellular Ca2+ mobilization and preventing the release of cytokines and chemokines from mast cells in a dose-dependent manner via the PKC-PLCγ-IP3R signaling pathway. CONCLUSION: In summary, HSYA has anti-anaphylactoid pharmacological activity, which makes it a potential candidate for the development of a novel agent to suppress drug-induced anaphylactoid reactions.

Spirostane-Type Saponins Obtained from Yucca schidigera.

It is well known that spirostane-type saponins show various bioactivities. In our on-going program of screening these kinds of constituents from natural products, Yucca schidigera was found to be rich in them, and nine new spirostanol saponins, Yucca spirostanosides A1 (1), A2 (2), B1 (3), B2 (4), B3 (5), C1 (6), C2 (7), C3 (8), and D1 (9), together with five known ones (10-14) were isolated from the plant. Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR and MS spectra, and comparing with published data.

Repair of a critical-size segmental rabbit femur defect using bioglass-ß-TCP monoblock, a vascularized periosteal flap and BMP-2.

Various synthetic bone substitutes are not suitable for reconstructing critical-size bone defects. This study tested whether a bioglass-ß-tricalcium phosphate (ß-TCP) monoblock is effective for repairing critical-size segmental bone defects if combined with a vascularized periosteal flap and bone morphogenetic protein (BMP)-2. A femoral osteotomy with a gap size of 20 mm was created and stabilized using a plate in 40 rabbits.The defect was left untreated (group A) or repaired using a monoblock (group B), a monoblock with a vascularized periosteal flap (group C), or a monoblock with a vascularized periosteal flap and BMP-2 (group D). Bone regeneration, vascularization and monoblock degradation were analyzed after four and eight weeks using x-ray, hematoxylin-eosin, CD34 immunohistochemical and Masson's trichrome staining observation and histometric evaluation. The radiographic grading score showed a time-dependent increase from weeks 4 to 8. At 8-week postoperative, the total new regenerated bone in groups C and D was 20.0 ± 0.3 and 55.5 ± 8.0 mm2 , respectively, which was significantly greater than in group B. Conversely, group D showed less residual monoblock than did group C. An increase in microvessel density was also observed in groups C and D compared with group B at 4 and 8 weeks postoperative, respectively. This study suggests that bioglass-ß-TCP monoblock alone exhibits poor potential to repair a 20-mm femoral defect. However, supplementation with a vascularized periosteal flap and BMP-2 led to effective vascularization and reliable bone regeneration throughout the monoblock, with concordant material degradation in a timely manner. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2148-2156, 2018.

Effects of paternal deprivation on cocaine-induced behavioral response and hypothalamic oxytocin immunoreactivity and serum oxytocin level in female mandarin voles.

Early paternal behavior plays a critical role in behavioral development in monogamous species. The vast majority of laboratory studies investigating the influence of parental behavior on cocaine vulnerability focus on the effects of early maternal separation. However, comparable studies on whether early paternal deprivation influences cocaine-induced behavioral response are substantially lacking. Mandarin vole (Microtus mandarinus) is a monogamous rodent with high levels of paternal care. After mandarin vole pups were subjected to early paternal deprivation, acute cocaine- induced locomotion, anxiety- like behavior and social behavior were examined in 45day old female pups, while hypothalamic oxytocin immunoreactivity and serum oxytocin level were also assessed. We found that cocaine increased locomotion and decreased social investigation, contact behavior and serum oxytocin level regardless of paternal care. Cocaine increased anxiety levels and decreased oxytocin immunoreactive neurons of the paraventricular nuclei and supraoptic nuclei in the bi-parental care group, whilst there were no specific effects in the paternal deprivation group. These results indicate that paternal deprivation results in different behavioral response to acute cocaine exposure in adolescents, which may be in part associated with the alterations in oxytocin immunoreactivity and peripheral OT level.

Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1.

T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of Th17 cells is mediated by the inhibition of SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation was strengthened in the animal model of experimental autoimmune encephalomyelitis (EAE). Moreover, we show that the reactive oxygen species (ROS) scavenger N-acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and exacerbates the severity of EAE. Thus, we have not only established MINK1 as a critical regulator of Th17 cell differentiation, but also clarified that accumulation of ROS may limit the generation of Th17 cells. The contribution of MINK1 to ROS-regulated Th17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements.

Neuronal activity and the expression of hypothalamic oxytocin and vasopressin in social versus cocaine conditioning.

Although drug rewards and natural rewards share neural substrates, the neuronal activation patterns and mechanisms behind the interaction between cocaine and social reward are poorly understood. Here, we investigated the conditioned place preference (CPP) in social (conspecific) vs cocaine conditioning, and the expression of central c-Fos, hypothalamic oxytocin (OT) and vasopressin (AVP) in ICR mice. We found that the mice produced CPP when conditioned with unfamiliar conspecific or cocaine alone. However, the mice failed to produce CPP when the two stimuli were concurrently conditioned. Compared to conditioning with conspecific alone, the mice decreased preference for conspecific when conditioning with social vs cocaine. We observed differential expression of c-Fos-immunoreactive neurons in the ventral anterior cingulate cortex, posterior cingulate cortex, accumbens (shell and core), medial nucleus of the amygdale and the ventral pallidum when comparing the control (CK), social (SC) or cocaine conditioning (CC) group, and social vs cocaine conditioning (SCC) group. Compared to the CK group, the SC or CC group had higher OT expression in the paraventricular nucleus (PVN) and lower AVP expression in the PVN and supraoptic nucleus. The SCC group showed lower OT expression compared to the SC group, and higher OT and AVP expression in the PVN compared to the CC group. These results indicate that cocaine impairs social preference through competing with social reward. The differential activations of neurons within specific reward areas, and differential expression of OT and AVP are likely to play an important role in mediating the interaction between social and cocaine rewards.

Paternal deprivation alters play-fighting, serum corticosterone and the expression of hypothalamic vasopressin and oxytocin in juvenile male mandarin voles.

Although early paternal deprivation significantly affects offspring behavioral and neuroendocrine development, the link between paternal deprivation and social play behavior remains unclear. Mandarin voles (Microtus mandarinus) are socially monogamous and display bi-paternal care. The present study examined the development of social play in juvenile male mandarin voles and the paternal influence on play-fighting, vasopressin- and oxytocin-immunoreactive neurons and serum corticosterone and testosterone levels. The results show that social play was more pronounced during postnatal days 28-35, differing from the ontogenetic pattern of other forms of social behavior. On postnatal day 35, the peak in play-fighting activity, paternal deprivation reduced boxing/wrestling levels and vasopressin-immunoreactive neurons in the anterior hypothalamus and oxytocin-immunoreactive neurons in the paraventricular nucleus, but increased vasopressin-immunoreactive neurons in the paraventricular nucleus and corticosterone levels. These results suggest that mandarin voles engage in social play according to an inverted U-shaped curve in ontogeny, and paternal deprivation influences the development of offspring play-fighting; hypothalamic vasopressin, oxytocin and serum corticosterone may play a modulatory role in the alteration of play-fighting elicited by paternal deprivation; decreased play-fighting may correlate with depressed vasopressin levels in the anterior hypothalamus.