Orders of magnitude loss reduction in photonic bandgap fibers by engineering the core surround.

We demonstrate how to reduce the loss in photonic bandgap fibers by orders of magnitude by varying the radius of the corner strands in the core surround. As a fundamental working principle we find that changing the corner strand radius can lead to backscattering of light into the fiber core. Selecting an optimal corner strand radius can thus reduce the loss of the fundamental core mode in a specific wavelength range by almost two orders of magnitude when compared to an unmodified cladding structure. Using the optimal corner radius for each transmission window, we observe the low-loss behavior for the first and second bandgaps, with the losses in the second bandgap being even lower than that of the first one. Our approach of reducing the confinement loss is conceptually applicable to all kinds of photonic bandgap fibers including hollow core and all-glass fibers as well as on-chip light cages. Therefore, our concept paves the way to low-loss light guidance in such systems with substantially reduced fabrication complexity.

Vastus intermedius vs vastus lateralis fascicle behaviors during maximal concentric and eccentric contractions.

Vastus intermedius (VI) plays a major role in knee extension, but its fascicle behaviors during dynamic contractions are not well understood. This study aimed to compare VI and vastus lateralis (VL) fascicle behaviors during singular maximal concentric and eccentric contractions. Thirteen men (27.1 ± 3.4 years) performed maximal isokinetic concentric contractions through knee joint angles of 105° to 35° (0° = full extension) and eccentric contractions from 35° to 105° at an angular velocity of 30°/s. Longitudinal VI and VL sonographic images were simultaneously recorded at 30 Hz, and muscle fascicle lengths at the knee joint angles of 40° and 100° were measured to compare the magnitudes of fascicle length change between the muscles. During concentric contractions, VI and VL fascicle lengths at 100° were 108 ± 12 mm and 104 ± 12 mm, respectively, and shortened by 36 ± 12 mm for VI and 28 ± 13 mm for VL (not statistically different; P = .13) at 40°. During eccentric contractions, VI and VL fascicle lengths at 40° were 72 ± 7 mm and 75 ± 8 mm, respectively, but lengthened by 35 ± 9 mm for VI and 24 ± 5 mm for VL at 100°, with a significant difference between the muscles (P = .01). These results indicate that VI fascicles are lengthened 1.4 times more than VL fascicles during eccentric contractions, whereas VI and VL fascicles shorten similarly during concentric contractions. This suggests a possibility that a greater mechanical strain is imposed to VI than VL during eccentric contractions.

Can the tricyanomethanide anion improve CO2 absorption by acetate-based ionic liquids?

Carbon dioxide absorption by mixtures of two ionic liquids with a common cation-1-butyl-3-methylimidazolium acetate, [C4C1Im][OAc], and 1-butyl-3-methylimidazolium tricyanomethanide, [C4C1Im][C(CN)3]-was determined experimentally at pressures below atmospheric pressure as a function of temperature between 303 K and 343 K, and at 303 K as a function of pressure up to 10 bar. It is observed that the absorption of carbon dioxide decreases with increasing tricyanomethanide anion concentration and with increasing temperature, showing a maximum of 0.4 mole fraction of carbon dioxide in pure [C4C1Im][OAc] at 303 K. At this temperature, the CO2 absorption in the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x is approximately the mole-fraction average of that in the pure ionic liquids. By applying an appropriate thermodynamic treatment, after identification of the species in solution, it was possible to calculate both the equilibrium constant, Keq, and Henry's law constant, KH, in the different mixtures studied thus obtaining an insight into the relative contribution of chemical and physical absorption of the gas. It is shown that chemical sorption proceeds through a 1 : 2 stoichiometry between CO2 and acetate-based ionic liquid. The presence of the C(CN)3- anion does not significantly affect the chemical reaction of the gas with the solvent (Keq = 75 ± 2 at 303 K) but leads to lower Henry's law constants (from KH = 77.8 ± 0.6 bar to KH = 49.5 ± 0.5 bar at 303 K), thus pointing towards larger physical absorption of the gas. The tricyanomethanide anion considerably improves the mass transfer by increasing the fluidity of the absorbent as proven by the larger diffusivities of all the ions when the concentration of the C(CN)3- anion increases in the mixtures.

Schizophrenia-like phenotypes in mice with NMDA receptor ablation in intralaminar thalamic nucleus cells and gene therapy-based reversal in adults.

In understanding the mechanism of schizophrenia pathogenesis, a significant finding is that drug abuse of phencyclidine or its analog ketamine causes symptoms similar to schizophrenia. Such drug effects are triggered even by administration at post-adolescent stages. Both drugs are N-methyl-d-aspartate receptor (NMDAR) antagonists, leading to a major hypothesis that glutamate hypofunction underlies schizophrenia pathogenesis. The precise region that depends on NMDAR function, however, is unclear. Here, we developed a mouse strain in which NMDARs in the intralaminar thalamic nuclei (ILN) were selectively disrupted. The mutant mice exhibited various schizophrenia-like phenotypes, including deficits in working memory, long-term spatial memory, and attention, as well as impulsivity, impaired prepulse inhibition, hyperlocomotion and hyperarousal. The electroencephalography analysis revealed that the mutant mice had a significantly reduced power in a wide range of frequencies including the alpha, beta and gamma bands, both during wake and rapid eye movement (REM) sleep, and a modest decrease of gamma power during non-REM sleep. Notably, restoring NMDARs in the adult ILN rescued some of the behavioral abnormalities. These findings suggest that NMDAR dysfunction in the ILN contributes to the pathophysiology of schizophrenia-related disorders. Furthermore, the reversal of inherent schizophrenia-like phenotypes in the adult mutant mice supports that ILN is a potential target site for a therapeutic strategy.

Tailoring the properties of acetate-based ionic liquids using the tricyanomethanide anion.

The equilibrium and transport properties of mixtures of two ionic liquids - [C4C1Im][OAc] and [C4C1Im][C(CN)3] - were determined and interpreted at the molecular level using vibration spectroscopy, NMR and molecular dynamics simulation. The non-ideality of the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x was characterized by V(E) = +0.28 cm(3) mol(-1) (293 K, x = 0.65) and H(E) = -2.2 kJ mol(-1) for x = 0.5. These values could be explained by a rearrangement of the hydrogen-bond network of the mixture that favours the interaction of the acetate anion with the imidazolium cation at position C2. The dynamic properties of the mixture are also dramatically influenced by the composition with a decrease of the viscosity and an increase of self-diffusion coefficients of the ions when the amount of tricyanomethanide anion increases in the mixture.

Reclaiming Our Lives in the Wake of a Nuclear Plant Accident.

Ryoko Ando lives and works in Iwaki-shi, which is located in the coastal area of Fukushima Prefecture. On 11 March 2011, Iwaki was hit by the Great East Japan Earthquake and tsunami. Then the nuclear plant accident at Fukushima No. 1 nuclear power plant, also located in the coastal area of Fukushima Prefecture, added to the woes of Iwaki residents. Although Iwaki-shi is outside of the 'restricted area' set up by the government in the 20 km radius around the nuclear power plant, some municipalities in Iwaki-shi lie within the 30 km radius zone. The residents of Iwaki were naturally concerned about the effects of radioactive contamination. On top of these, they had to confront a wide range of issues, including confusion and miscommunication, reputation risk and infrastructural constraints due to the influx of residents from the 'restricted area'.

Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea.

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) (n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes.

Ethos in Fukushima and the ICRP dialogue seminars.

Ethos in Fukushima, a non-profit organisation, participated in 10 of the 12 International Commission on Radiological Protection (ICRP) dialogue seminars over the past 4 years. The slides and videos that were shown at the seminars are recorded on the Ethos in Fukushima website ( http://ethos-fukushima.blogspot.jp/p/icrp-dialogue.html ). I would like to introduce the activities of Ethos in Fukushima to date, and explain why the ICRP dialogue materials have come to be published on its website.

Measuring, discussing, and living together: lessons from 4 years in Suetsugi.

Cooperating with radiological protection experts and taking radiation measurements, the residents of Suetsugi, Iwaki City, Fukushima have been striving to reshape their lives since the accident at Fukushima Daiichi nuclear power plant. Suetsugi lies within 30 km of the power plant, so the residents have had serious reservations about continuing their lives there since the accident. Today, radiation remains a 'line' dividing their lives, with any dose measurements directly affecting their daily decision making. Assisted by medical and scientific specialists, the residents faced this challenging situation by measuring exposures individually and then discussing the results among themselves. Since 2012, the residents of Suetsugi have been using personal dosimeters, made village-wide trips for whole-body counter tests, and measured food contamination throughout the village. The results have been shared openly between the residents. Obtaining and discussing their own data were crucial to gain understanding of various results and to practice radiological protection in their daily routine. These 4 y of experience in Suetsugi demonstrate cooperation between various stakeholders, which should be a lesson for the future.

Protective effect of rasagiline in aminoglycoside ototoxicity.

Sensorineural hearing losses (SNHLs; e.g., ototoxicant- and noise-induced hearing loss or presbycusis) are among the most frequent sensory deficits, but they lack effective drug therapies. The majority of recent therapeutic approaches focused on the trials of antioxidants and reactive oxygen species (ROS) scavengers in SNHLs. The rationale for these studies was the prominent role of disturbed redox homeostasis and the consequent ROS elevation. Although the antioxidant therapies in several animal studies seemed to be promising, clinical trials have failed to fulfill expectations. We investigated the potential of rasagiline, an FDA-approved monomanine oxidase type B inhibitor (MAO-B) inhibitor type anti-parkinsonian drug, as an otoprotectant. We showed a dose-dependent alleviation of the kanamycin-induced threshold shifts measured by auditory brainstem response (ABR) in an ototoxicant aminoglycoside antibiotic-based hearing loss model in mice. This effect proved to be statistically significant at a 6-mg/kg (s.c.) dose. The most prominent effect appeared at 16kHz, which is the hearing sensitivity optimum for mice. The neuroprotective, antiapoptotic and antioxidant effects of rasagiline in animal models, all targeting a specific mechanism of aminoglycoside injury, may explain this otoprotection. The dopaminergic neurotransmission enhancer effect of rasagiline might also contribute to the protection. Dopamine (DA), released from lateral olivocochlear (LOC) fibers, was shown to exert a protective action against excitotoxicity, a pathological factor in the aminoglycoside-induced SNHL. We have shown that rasagiline enhanced the electric stimulation-evoked release of DA from an acute mouse cochlea preparation in a dose-dependent manner. Using inhibitors of voltage-gated Na(+)-, Ca(2+) channels and DA transporters, we revealed that rasagiline potentiated the action potential-evoked release of DA by inhibiting the reuptake. The complex, multifactorial pathomechanism of SNHLs most likely requires drugs acting on multiple targets for effective therapy. Rasagiline, with its multi-target action and favorable adverse effects profile, might be a good candidate for a clinical trial testing the otoprotective indication.

K+ depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: a microelectrode biosensor study.

BACKGROUND AND PURPOSE: This study was undertaken to characterize the ATP, adenosine and glutamate outflow evoked by depolarization with high K(+) concentrations, in slices of rat hippocampus. EXPERIMENTAL APPROACH: We utilized the microelectrode biosensor technique and extracellular electrophysiological recording for the real-time monitoring of the efflux of ATP, adenosine and glutamate. KEY RESULTS: ATP, adenosine and glutamate sensors exhibited transient and reversible current during depolarization with 25 mM K(+) , with distinct kinetics. The ecto-ATPase inhibitor ARL67156 enhanced the extracellular level of ATP and inhibited the prolonged adenosine efflux, suggesting that generation of adenosine may derive from the extracellular breakdown of ATP. Stimulation-evoked ATP, adenosine and glutamate efflux was inhibited by tetrodotoxin, while exposure to Ca(2+) -free medium abolished ATP and adenosine efflux from hippocampal slices. Extracellular elevation of ATP and adenosine were decreased in the presence of NMDA receptor antagonists, D-AP-5 and ifenprodil, whereas non-NMDA receptor blockade by CNQX inhibited glutamate but not ATP and adenosine efflux. The gliotoxin fluoroacetate and P2X7 receptor antagonists inhibited the K(+) -evoked ATP, adenosine and glutamate efflux, while carbenoxolone in low concentration and probenecid decreased only the adenosine efflux. CONCLUSIONS AND IMPLICATIONS: Our results demonstrated activity-dependent gliotransmitter release in the hippocampus in response to ongoing neuronal activity. ATP and glutamate were released by P2X7 receptor activation into extracellular space. Although the increased extracellular levels of adenosine did derive from released ATP, adenosine might also be released directly via pannexin hemichannels.

A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain.

BACKGROUND AND PURPOSE: This study was undertaken to compare the analgesic activity of antagonists acting at P2X1, P2X7, and P2Y12 receptors and agonists acting at P2Y1, P2Y2, P2Y4, and P2Y6 receptors in neuropathic, acute, and inflammatory pain. EXPERIMENTAL APPROACH: The effect of the wide spectrum P2 receptor antagonist PPADS, the selective P2X7 receptor antagonist Brilliant Blue G (BBG), the P2X1 receptor antagonist (4,4',4'',4-[carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid, octasodium salt (NF449) and (8,8'-[carbonylbis(imino-3,1-phenylenecarbonylimino)]bis-1,3,5-naphthalene-trisulphonic acid, hexasodium salt (NF023), the P2Y12 receptor antagonist (2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-propionyloxymethyl)-propylester (MRS2395), the selective P2Y1 receptor agonist ([[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid mono ester trisodium salt (MRS2365), the P2Y2/P2Y4 agonist uridine-5'-triphosphate (UTP), and the P2Y4/P2Y6 agonist uridine-5'-diphosphate (UDP) were examined on mechanical allodynia in the Seltzer model of neuropathic pain, on acute thermal nociception, and on the inflammatory pain and oedema induced by complete Freund's adjuvant (CFA). KEY RESULTS: MRS2365, MRS2395 and UTP, but not the other compounds, significantly alleviated mechanical allodynia in the neuropathic pain model, with the following rank order of minimal effective dose (mED) values: MRS2365 > MRS2395 > UTP. All compounds had a dose-dependent analgesic action in acute pain except BBG, which elicited hyperalgesia at a single dose. The rank order of mED values in acute pain was the following: MRS2365 > MRS2395 > NF449 > NF023 > UDP = UTP > PPADS. MRS2365 and MRS2395 had a profound, while BBG had a mild effect on inflammatory pain, with a following rank order of mED values: MRS2395 > MRS2365 > BBG. None of the tested compounds had significant action on oedema evoked by intraplantar injection of CFA. CONCLUSIONS AND IMPLICATIONS: Our results show that antagonism at P2X1, P2Y12, and P2X7 receptors and agonism at P2Y1 receptors define promising therapeutic strategies in acute, neuropathic, and inflammatory pain respectively.

Heat-moisture treatment of high-amylose corn starch increases dietary fiber content and lowers plasma cholesterol in ovariectomized rats.

The effect of dietary high-amylose corn starch (HACS) of varying dietary fiber (DF) content on plasma cholesterol was examined in ovariectomized (OVX) rats. Gelatinized normal corn starch (G-CS) was used as a reference. OVX rats were fed a fiber-free purified diet containing G-CS, HACS, gelatinized high-amylose corn starch (G-HACS), or heat-moisture treated HACS (HM-HACS) at 400 g starch/kg diet for 21 d. The DF content of G-CS, HACS, G-HACS, and HM-HACS measured by the AOAC method was 0.1, 19.3, 2.4, and 64.5 g/100 g, respectively. The dry weight of cecal contents, cecal wall weight, the amount of short chain fatty acids in cecal contents, the amount of bile acids in small intestinal contents, and fecal excretion of neutral sterols increased logarithmically with increasing DF, while total plasma cholesterol concentration decreased. On the other hand, hepatic CYP7A1 activity, fecal dry weight, and fecal excretion of bile acids increased linearly with increasing DF, while body weight gain decreased. The hypocholesterolemic effect of HACS in OVX-rats appeared to be more effective by heat-moisture treatment.

Single dose of MDMA causes extensive decrement of serotoninergic fibre density without blockage of the fast axonal transport in Dark Agouti rat brain and spinal cord.

Prolonged neurotoxicity of the recreational drug, MDMA (3,4-methylenedioxymethamphetamine) on serotoninergic axon terminals has been suggested. The effect of a single (15 mg/kg) dose of intraperitoneally administered MDMA on serotoninergic fibre density, defined by tryptophan hydroxylase (TpH) and serotonin transporter (5-HTT) immunoreactivity, has been evaluated in the spinal cord and brain areas in Dark Agouti rats, 7 and 180 days after MDMA applications. Immunostaining for amyloid precursor protein (APP) has been performed to examine possible defects of the fast axonal transport, and 5-HTT mRNA expressions were quantified in neurones of medullary raphe nuclei. Seven days after MDMA treatment, a substantial decrease in the density of TpH-immunoreactive fibres was detectable in the frontal cortex, the caudate-putamen, the CA1 region of the hippocampus, and marked decreases were found in the spinal cord. These changes in TpH density showed a high correlation with 5-HTT densities. In contrast, APP-immunoreactive axonal bulbs were not detected in any of the brain regions studied. Seven days after MDMA administrations, significantly elevated 5-HTT mRNA expressions were found in the raphe pallidus and obscurus. Our results suggest that a single dose of MDMA elicits widespread depletion of TpH and 5-HTT immunoreactivity in serotoninergic axons without morphological sign of the blockage of the fast anterograde axonal transport. Our results do not support the notion of MDMA-induced axotomy of serotoninergic neurones. The up-regulation of 5-HTT mRNA expressions 1 week after MDMA injections might indicate the potential recovery of the serotonin system.

Increase of galanin in trigeminal ganglion during tooth movement.

It is known that nerve fibers containing neuropeptides such as galanin increase in the periodontal ligament during experimental tooth movement. However, the origin of galanin-containing nerve fibers in the periodontal ligament remains unclear. This study was conducted to examine our hypothesis that the increased galanin nerve fibers have a sensory neuronal origin, and that the peptide is associated with pain transmission and/or periodontal ligament remodeling during experimental tooth movement. In control rats, galanin-immunoreactive trigeminal ganglion cells were very rare and were observed predominantly in small ganglion cells. After 3 days of experimental tooth movement, galanin-immunoreactive trigeminal ganglion cells significantly increased, and the most marked increase was observed at 5 days after experimental tooth movement. Furthermore, their cell size spectrum also significantly changed after 3 and 5 days of movement: Medium-sized and large trigeminal ganglion cells began expressing, and continued to express, galanin until 14 days after experimental tooth movement. These findings suggest that the increase of galanin in the periodontal ligament during experimental tooth movement at least partially originates from trigeminal ganglion neurons and may play a role in pain transmission and/or periodontal remodeling.

Characteristics of propofol-evoked vascular pain in anaesthetized rats.

BACKGROUND: In this study we have assessed vascular pain caused by the i.v. anaesthetic agent, propofol, using the flexor reflex response and compared this with that of capsaicin in anaesthetized intact rats. METHODS: Experiments were performed on 133 male Sprague-Dawley rats weighing 280-340 g. The animals were anaesthetized with urethane (1.3 g kg(-1), i.p.), and an arterial cannula was inserted to the level of the bifurcation of the femoral artery. The magnitude of the flexor reflex was examined by recording the electromyogram from the posterior biceps femoris/semitendinosus muscles. RESULTS: Our data show that the flexor reflexes evoked by intra-arterial (i.a.) injection of propofol (1%, 25-100 microl) and capsaicin (0.05-0.2 microg) were dose dependent. An initial i.a. injection of procaine (2%, 200 microl) blocked both responses. Furthermore, the flexor reflex induced by these chemical stimuli were inhibited by morphine (5 mg kg(-1), s.c.) and restored with naloxone (1.5 mg kg(-1), s.c.). Pre-treatment with capsazepine (20 microg, i.a.), a selective VR1 antagonist, inhibited the capsaicin-evoked response, but not that of propofol. Indomethacin (10 mg kg(-1), i.p.), a non-selective cyclo-oxygenase inhibitor, inhibited only the propofol-evoked response and this recovered with arterial PGE2 (5 microg). CONCLUSIONS: Collectively our data suggest that propofol-evoked vascular pain is mainly initiated by prostanoids.

Contribution of brominated organic disinfection by-products to the mutagenicity of drinking water.

The activity inducing chromosomal aberrations of the mixture of brominated disinfection by-products (DBPs) was approximately three times higher than that of the chlorinated counterparts for the same hypohalous acid dose. With the combination of chromosomal aberration test and a new analytical technique to differentiate total organic chlorine (TOCl) and total organic bromine (TOBr), it was found that TOBr was correlated to the mutagenicity of chlorinated waters. It was also implied that for a bromide-to-TOC ratio of 0.1 (mg/mg C), brominated DBPs could account for at least 29% of the total toxicity of DBPs formed during chlorination. On the other hand, bromate ion, a major ozonation DBP, was not a major contributor to the activity inducing chromosomal aberrations of the water treated with an ozone/chlorine sequential process. Therefore, ozonation is one possible option to reduce the health risk caused by DBPs even in the presence of bromide.

An assessment of vascular pain using the flexor reflex in anesthetized rats.

This study assessed the flexor reflex induced by intraarterial algogenic drugs in anesthetized rats. The experiments were performed on male Sprague Dawley rats weighing 290-350 g. The animals were anesthetized with urethane (1.3 g/kg i.p.) and an arterial cannula was inserted to the level of the bifurcation of the femoral artery. The magnitude of the flexor reflex was examined by recording the electromyograph from the posterior biceps femoris/semitendinous muscles. Results showed that the flexor reflex evoked by intra-arterial injection of capsaicin (0.05-0.5 microg) was dose-dependent. A similar reflex resulted from pinching the toe of the hindlimb. These responses were inhibited by morphine (5 mg/kg s.c.) and restored with naloxone (1.5 mg/kg s.c.). Intraarterial preinjection of procaine (2%, 200 microl) and capsazepine (20 microg), which is a selective vanilloid receptor antagonist, inhibited the capsaicin-evoked response, but not that of pinching. These results indicate that the flexor reflex is a useful tool for assessing vascular pain in anesthetized animals.

Differential effects of yohimbine, naloxone and 8-OH-DPAT on ejaculatory response in male dogs.

The aim of this study was to compare the effects of the alpha(2)-adrenergic-receptor antagonist yohimbine, the 5-HT(lA)-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the opioid-receptor antagonist naloxone (all of which have been shown to stimulate male sexual arousal/motivation in rats) on sexual responses in male dogs. Sexual responses (i.e., ejaculation, penile erection and pelvic thrusting behavior) were elicited by manual penile stimulation. Systemic administration of yohimbine (0.03-1.0 mg/kg) produced a biphasic dose response curve for the amount of ejaculated semen collected during genital stimulation (for 5 min), whereas 8-OH-DPAT (0.03-0.3 mg/kg) dose-dependently decreased the amount of ejaculated semen. Thus, yohimbine increased the amount of ejaculated semen at lower doses (0.03-0.3 mg/kg), but decreased it at the highest dose (1.0 mg/kg). The highest dose of yohimbine (1.0 mg/kg) and 8-OH-DPAT (0.3 mg/kg) also produced a significant delay of onset in both ejaculation and penile erection latency (time from starting the stimulation to the first ejaculation and full erection), and a decrease in the incidence of pelvic thrusting behavior. In contrast, administration of naloxone (0.03-1.0 mg/kg) did not affect the sexual responses elicited by genital stimulation. These results indicate that yohimbine and 8-OH-DPAT, but not naloxone, affect sexual responses, particularly ejaculation, and that the drugs which stimulate the mechanisms regulating sexual arousal/motivation in male rats do not show identical effects for sexual function in male dogs. The present findings also confirm our previous observations that the ejaculatory capacity in dogs can be stimulated by lower doses of yohimbine, as evidenced by an increase in the amount of ejaculated semen.